rs34682727

Positions:

chr14-88426674-G-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_018418.5(SPATA7):c.815G>A(p.Arg272Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000375 in 1,613,280 control chromosomes in the GnomAD database, including 1 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R272W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00020 ( 1 hom. )

Consequence

SPATA7
NM_018418.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:2

Conservation

PhyloP100: -0.290

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0026152432).

BP6

Variant 14-88426674-G-A is Benign according to our data. Variant chr14-88426674-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 198231.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=2}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPATA7	NM_018418.5 linkuse as main transcript	c.815G>A	p.Arg272Gln	missense_variant	6/12	ENST00000393545.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPATA7	ENST00000393545.9 linkuse as main transcript	c.815G>A	p.Arg272Gln	missense_variant	6/12	1	NM_018418.5	P2	Q9P0W8-1

Frequencies

GnomAD3 genomes

AF:

0.00202

AC:

307

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00705

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000530

AC:

131

AN:

247138

Hom.:

AF XY:

0.000394

AC XY:

AN XY:

134570

show subpopulations

Gnomad AFR exome

AF:

0.00713

Gnomad AMR exome

AF:

0.000406

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0000470

Gnomad NFE exome

AF:

0.0000270

Gnomad OTH exome

AF:

0.000496

GnomAD4 exome

AF:

0.000203

AC:

297

AN:

1461052

Hom.:

Cov.:

AF XY:

0.000176

AC XY:

128

AN XY:

726858

show subpopulations

Gnomad4 AFR exome

AF:

0.00702

Gnomad4 AMR exome

AF:

0.000559

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.000414

GnomAD4 genome

AF:

0.00202

AC:

308

AN:

152228

Hom.:

Cov.:

AF XY:

0.00202

AC XY:

150

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.00705

Gnomad4 AMR

AF:

0.000589

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000363

Hom.:

Bravo

AF:

0.00242

ESP6500AA

AF:

0.00528

AC:

ESP6500EA

AF:

0.000120

AC:

ExAC

AF:

0.000694

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Leber congenital amaurosis 3

Uncertain:1Benign:1

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 03, 2024	- -
Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Retinitis pigmentosa

Uncertain:1

Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

May 24, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.0075

.;T;.;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.84

.;T;T;T

M_CAP

Benign

0.0017

MetaRNN

Benign

0.0026

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.89

.;L;.;L

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.20

PROVEAN

Benign

0.25

N;N;N;N

REVEL

Benign

0.010

Sift

Benign

0.39

T;T;T;T

Sift4G

Benign

0.56

T;T;T;T

Polyphen

0.038

B;B;B;.

Vest4

0.091

MVP

0.040

MPC

0.12

ClinPred

0.00056

GERP RS

-3.9

Varity_R

0.031

gMVP

0.22

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

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