Genetic Variant SPATA31D3:p.Glu755Lys (chr9-81947516-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_207416.3(SPATA31D3):c.2263G>A(p.Glu755Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 9/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000017 ( 0 hom., cov: 20)

Exomes 𝑓: 0.000048 ( 3 hom. )

Failed GnomAD Quality Control

Consequence

SPATA31D3
NM_207416.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.118

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.036027223).

BP6

Variant 9-81947516-G-A is Benign according to our data. Variant chr9-81947516-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3800406.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA31D3	NM_207416.3 link	c.2263G>A	p.Glu755Lys	missense_variant	Exon 4 of 4	ENST00000445385.3	NP_997299.2	P0C874
LOC105376105	NR_188610.1 link	n.943-1030C>T		intron_variant	Intron 3 of 5
LOC105376105	NR_188611.1 link	n.943-1030C>T		intron_variant	Intron 3 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SPATA31D3	ENST00000445385.3 link	c.2263G>A	p.Glu755Lys	missense_variant	Exon 4 of 4	1	NM_207416.3	ENSP00000488117.1	P0C874
ENSG00000267559	ENST00000585776.5 link	n.943-1030C>T		intron_variant	Intron 3 of 4	2
ENSG00000267559	ENST00000592744.1 link	n.519-1030C>T		intron_variant	Intron 3 of 3	4

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

120984

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000326

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000171

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000594

AC:

AN:

134692

Hom.:

AF XY:

0.0000841

AC XY:

AN XY:

71310

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000486

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000316

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000261

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000485

AC:

AN:

1382204

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

685002

show subpopulations

Gnomad4 AFR exome

AF:

0.0000325

Gnomad4 AMR exome

AF:

0.0000813

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000578

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000132

Gnomad4 OTH exome

AF:

0.0000521

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000165

AC:

AN:

121052

Hom.:

Cov.:

AF XY:

0.0000172

AC XY:

AN XY:

57978

show subpopulations

Gnomad4 AFR

AF:

0.0000325

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000171

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000429

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 21, 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

0.073

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.8

DANN

Benign

0.41

DEOGEN2

Benign

0.0033

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.59

MetaRNN

Benign

0.036

MutationAssessor

Benign

0.79

PrimateAI

Benign

0.44

Sift4G

Benign

0.42

Polyphen

0.034

Vest4

0.13

GERP RS

1.1

Varity_R

0.029

gMVP

0.13

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