14-88385822-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018418.5(SPATA7):c.4G>A(p.Asp2Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 1,604,026 control chromosomes in the GnomAD database, including 126,073 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D2H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.31 ( 9059 hom., cov: 33)

Exomes 𝑓: 0.39 ( 117014 hom. )

Consequence

SPATA7
NM_018418.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.251

Publications

37 publications found

Variant links:

Genes affected

SPATA7 (HGNC:20423): (spermatogenesis associated 7) This gene, originally isolated from testis, is also expressed in retina. Mutations in this gene are associated with Leber congenital amaurosis and juvenile retinitis pigmentosa. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2010]

SPATA7 Gene-Disease associations (from GenCC):

Leber congenital amaurosis 3
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
Leber congenital amaurosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
severe early-childhood-onset retinal dystrophy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SPATA7 links:

ENSG00000296360 (HGNC:):

ENSG00000296360 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.6560168E-4).

BP6

Variant 14-88385822-G-A is Benign according to our data. Variant chr14-88385822-G-A is described in ClinVar as [Benign]. Clinvar id is 95907.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA7	NM_018418.5 link	c.4G>A	p.Asp2Asn	missense_variant	Exon 1 of 12	ENST00000393545.9	NP_060888.2	Q9P0W8-1V9HVY9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA7	ENST00000393545.9 link	c.4G>A	p.Asp2Asn	missense_variant	Exon 1 of 12	1	NM_018418.5	ENSP00000377176.4		Q9P0W8-1

Frequencies

GnomAD3 genomes

AF:

0.307

AC:

46699

AN:

152020

Hom.:

9063

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0974

Gnomad AMI

AF:

0.334

Gnomad AMR

AF:

0.278

Gnomad ASJ

AF:

0.401

Gnomad EAS

AF:

0.0427

Gnomad SAS

AF:

0.260

Gnomad FIN

AF:

0.528

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.423

Gnomad OTH

AF:

0.355

GnomAD2 exomes

AF:

0.329

AC:

76069

AN:

231254

AF XY:

0.337

show subpopulations

Gnomad AFR exome

AF:

0.0878

Gnomad AMR exome

AF:

0.217

Gnomad ASJ exome

AF:

0.400

Gnomad EAS exome

AF:

0.0341

Gnomad FIN exome

AF:

0.521

Gnomad NFE exome

AF:

0.422

Gnomad OTH exome

AF:

0.384

GnomAD4 exome

AF:

0.389

AC:

565174

AN:

1451888

Hom.:

117014

Cov.:

AF XY:

0.388

AC XY:

279820

AN XY:

721190

show subpopulations

African (AFR)

AF:

0.0816

AC:

2731

AN:

33448

American (AMR)

AF:

0.226

AC:

9850

AN:

43560

Ashkenazi Jewish (ASJ)

AF:

0.402

AC:

10403

AN:

25872

East Asian (EAS)

AF:

0.0420

AC:

1655

AN:

39394

South Asian (SAS)

AF:

0.267

AC:

22502

AN:

84432

European-Finnish (FIN)

AF:

0.518

AC:

26904

AN:

51958

Middle Eastern (MID)

AF:

0.435

AC:

2483

AN:

5708

European-Non Finnish (NFE)

AF:

0.422

AC:

467069

AN:

1107534

Other (OTH)

AF:

0.360

AC:

21577

AN:

59982

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

17418

34836

52255

69673

87091

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.307

AC:

46675

AN:

152138

Hom.:

9059

Cov.:

AF XY:

0.311

AC XY:

23123

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.0972

AC:

4039

AN:

41560

American (AMR)

AF:

0.278

AC:

4250

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.401

AC:

1389

AN:

3462

East Asian (EAS)

AF:

0.0424

AC:

219

AN:

5162

South Asian (SAS)

AF:

0.260

AC:

1255

AN:

4830

European-Finnish (FIN)

AF:

0.528

AC:

5582

AN:

10572

Middle Eastern (MID)

AF:

0.439

AC:

129

AN:

294

European-Non Finnish (NFE)

AF:

0.423

AC:

28770

AN:

67942

Other (OTH)

AF:

0.350

AC:

739

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1508

3017

4525

6034

7542

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.385

Hom.:

24799

Bravo

AF:

0.276

TwinsUK

AF:

0.417

AC:

1547

ALSPAC

AF:

0.426

AC:

1643

ESP6500AA

AF:

0.106

AC:

466

ESP6500EA

AF:

0.391

AC:

3358

ExAC

AF:

0.317

AC:

38241

Asia WGS

AF:

0.147

AC:

510

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Aug 20, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Leber congenital amaurosis 3

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Retinal dystrophy

Benign:1

Oct 01, 2023

Dept Of Ophthalmology, Nagoya University

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

- -

Retinitis pigmentosa

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0097

.;T;.;T;T;.

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.079

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.73

.;T;T;T;T;T

MetaRNN

Benign

0.00047

T;T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.90

L;L;L;.;.;L

PhyloP100

0.25

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.62

N;N;N;N;N;N

REVEL

Benign

0.055

Sift

Benign

0.058

T;T;T;D;D;T

Sift4G

Benign

0.21

T;T;T;.;T;T

Polyphen

0.015

B;P;B;.;.;.

Vest4

0.038

MPC

0.14

ClinPred

0.039

GERP RS

2.2

PromoterAI

-0.12

Neutral

(source)

Varity_R

0.059

gMVP

0.13

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

14-88385822-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over