rs3179969

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.220G>A(p.Val74Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 1,604,060 control chromosomes in the GnomAD database, including 98,114 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 12205 hom., cov: 32)

Exomes 𝑓: 0.34 ( 85909 hom. )

Consequence

SPATA7
NM_018418.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 1.07

Publications

47 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:

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=2.2908449E-5).

BP6

Variant 14-88396185-G-A is Benign according to our data. Variant chr14-88396185-G-A is described in ClinVar as Benign. ClinVar VariationId is 286866.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA7	NM_018418.5 link	c.220G>A	p.Val74Met	missense_variant	Exon 4 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.220G>A	p.Val74Met	missense_variant	Exon 4 of 12	1	NM_018418.5	ENSP00000377176.4		Q9P0W8-1

Frequencies

GnomAD3 genomes

AF:

0.387

AC:

58689

AN:

151648

Hom.:

12175

Cov.:

show subpopulations

Gnomad AFR

AF:

0.539

Gnomad AMI

AF:

0.420

Gnomad AMR

AF:

0.275

Gnomad ASJ

AF:

0.330

Gnomad EAS

AF:

0.331

Gnomad SAS

AF:

0.420

Gnomad FIN

AF:

0.285

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.342

Gnomad OTH

AF:

0.344

GnomAD2 exomes

AF:

0.337

AC:

84495

AN:

250882

AF XY:

0.337

show subpopulations

Gnomad AFR exome

AF:

0.547

Gnomad AMR exome

AF:

0.234

Gnomad ASJ exome

AF:

0.335

Gnomad EAS exome

AF:

0.320

Gnomad FIN exome

AF:

0.280

Gnomad NFE exome

AF:

0.337

Gnomad OTH exome

AF:

0.315

GnomAD4 exome

AF:

0.339

AC:

492221

AN:

1452296

Hom.:

85909

Cov.:

AF XY:

0.340

AC XY:

245935

AN XY:

722918

show subpopulations

African (AFR)

AF:

0.549

AC:

18192

AN:

33130

American (AMR)

AF:

0.244

AC:

10880

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.333

AC:

8681

AN:

26048

East Asian (EAS)

AF:

0.302

AC:

11946

AN:

39580

South Asian (SAS)

AF:

0.391

AC:

33637

AN:

85968

European-Finnish (FIN)

AF:

0.284

AC:

15147

AN:

53386

Middle Eastern (MID)

AF:

0.276

AC:

1284

AN:

4654

European-Non Finnish (NFE)

AF:

0.336

AC:

371700

AN:

1104932

Other (OTH)

AF:

0.346

AC:

20754

AN:

59920

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

15050

30100

45149

60199

75249

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12010

24020

36030

48040

60050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.387

AC:

58790

AN:

151764

Hom.:

12205

Cov.:

AF XY:

0.380

AC XY:

28204

AN XY:

74136

show subpopulations

African (AFR)

AF:

0.540

AC:

22331

AN:

41388

American (AMR)

AF:

0.276

AC:

4207

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.330

AC:

1144

AN:

3464

East Asian (EAS)

AF:

0.332

AC:

1711

AN:

5158

South Asian (SAS)

AF:

0.420

AC:

2022

AN:

4810

European-Finnish (FIN)

AF:

0.285

AC:

2986

AN:

10474

Middle Eastern (MID)

AF:

0.279

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.342

AC:

23194

AN:

67894

Other (OTH)

AF:

0.347

AC:

731

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1786

3571

5357

7142

8928

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

552

1104

1656

2208

2760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.350

Hom.:

42234

Bravo

AF:

0.391

TwinsUK

AF:

0.330

AC:

1225

ALSPAC

AF:

0.338

AC:

1302

ESP6500AA

AF:

0.544

AC:

2396

ESP6500EA

AF:

0.343

AC:

2948

ExAC

AF:

0.346

AC:

42053

Asia WGS

AF:

0.387

AC:

1346

AN:

3476

EpiCase

AF:

0.329

EpiControl

AF:

0.325

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Leber congenital amaurosis 3

Benign:3

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 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. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Apr 04, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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 12, 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

0.065

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.0032

.;T;.;T;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.11

.;T;T;T;T;T

MetaRNN

Benign

0.000023

T;T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.1

.;N;.;.;.;N

PhyloP100

1.1

PrimateAI

Benign

0.34

PROVEAN

Benign

1.1

N;N;N;N;N;N

REVEL

Benign

0.067

Sift

Benign

1.0

T;T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T;T

Polyphen

0.0010

B;B;B;.;.;.

Vest4

0.11

MPC

0.095

ClinPred

0.0065

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.020

gMVP

0.041

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

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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