Genetic Variant SPATA31D3:p.Asn714Ser (chr9-81947394-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_207416.3(SPATA31D3):c.2141A>G(p.Asn714Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 8/12 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 9)

Exomes 𝑓: 0.00011 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SPATA31D3
NM_207416.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.87

Variant links:

Genes affected

SPATA31D3 (HGNC:38603): (SPATA31 subfamily D member 3) Predicted to be involved in cell differentiation and spermatogenesis. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SPATA31D3 links:

ENSG00000267559 (HGNC:):

ENSG00000267559 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010542542).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA31D3	NM_207416.3 link	c.2141A>G	p.Asn714Ser	missense_variant	Exon 4 of 4	ENST00000445385.3	NP_997299.2	P0C874
LOC105376105	NR_188610.1 link	n.943-908T>C		intron_variant	Intron 3 of 5
LOC105376105	NR_188611.1 link	n.943-908T>C		intron_variant	Intron 3 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SPATA31D3	ENST00000445385.3 link	c.2141A>G	p.Asn714Ser	missense_variant	Exon 4 of 4	1	NM_207416.3	ENSP00000488117.1	P0C874
ENSG00000267559	ENST00000585776.5 link	n.943-908T>C		intron_variant	Intron 3 of 4	2
ENSG00000267559	ENST00000592744.1 link	n.519-908T>C		intron_variant	Intron 3 of 3	4

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

71272

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000621

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00299

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000112

AC:

109

AN:

973536

Hom.:

Cov.:

AF XY:

0.000158

AC XY:

AN XY:

488318

show subpopulations

Gnomad4 AFR exome

AF:

0.0000902

Gnomad4 AMR exome

AF:

0.0000707

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000622

Gnomad4 SAS exome

AF:

0.00122

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000292

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000210

AC:

AN:

71338

Hom.:

Cov.:

AF XY:

0.000151

AC XY:

AN XY:

33034

show subpopulations

Gnomad4 AFR

AF:

0.000618

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00300

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000972

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 20, 2025

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.0070

DANN

Benign

0.32

DEOGEN2

Benign

0.00077

FATHMM_MKL

Benign

0.00027

LIST_S2

Benign

0.22

MetaRNN

Benign

0.011

MutationAssessor

Benign

-1.2

PrimateAI

Uncertain

0.50

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.013

GERP RS

-1.7

Varity_R

0.049

gMVP

0.016

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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