14-88385822-G-A

Position:

chr14-88385822-G-A

Variant summary

Our verdict is Benign. Variant got -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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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

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 links:

SPATA7 (HGNC:):

SPATA7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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. Variant chr14-88385822-G-A is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
SPATA7	NM_018418.5 linkuse as main transcript	c.4G>A	p.Asp2Asn	missense_variant	1/12	ENST00000393545.9	NP_060888.2	Q9P0W8-1V9HVY9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPATA7	ENST00000393545.9 linkuse as main transcript	c.4G>A	p.Asp2Asn	missense_variant	1/12	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

GnomAD3 exomes

AF:

0.329

AC:

76069

AN:

231254

Hom.:

14853

AF XY:

0.337

AC XY:

42249

AN XY:

125228

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 SAS exome

AF:

0.260

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

Gnomad4 AFR exome

AF:

0.0816

Gnomad4 AMR exome

AF:

0.226

Gnomad4 ASJ exome

AF:

0.402

Gnomad4 EAS exome

AF:

0.0420

Gnomad4 SAS exome

AF:

0.267

Gnomad4 FIN exome

AF:

0.518

Gnomad4 NFE exome

AF:

0.422

Gnomad4 OTH exome

AF:

0.360

GnomAD4 genome

AF:

0.307

AC:

46675

AN:

152138

Hom.:

9059

Cov.:

AF XY:

0.311

AC XY:

23123

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.0972

Gnomad4 AMR

AF:

0.278

Gnomad4 ASJ

AF:

0.401

Gnomad4 EAS

AF:

0.0424

Gnomad4 SAS

AF:

0.260

Gnomad4 FIN

AF:

0.528

Gnomad4 NFE

AF:

0.423

Gnomad4 OTH

AF:

0.350

Alfa

AF:

0.386

Hom.:

9491

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

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 20, 2013	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Leber congenital amaurosis 3

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Retinal dystrophy

Benign:1

Benign, criteria provided, single submitter

research

Dept Of Ophthalmology, Nagoya University

Oct 01, 2023

- -

Retinitis pigmentosa

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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. -

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

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

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

Varity_R

0.059

gMVP

0.13

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over