Genetic Variant SPATA31D3:p.Arg695Cys (chr9-81947336-C-T) – 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.2083C>T(p.Arg695Cys) 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000021 ( 0 hom., cov: 6)

Exomes 𝑓: 0.000048 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SPATA31D3
NM_207416.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.331

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=0.022995353).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA31D3	NM_207416.3 link	c.2083C>T	p.Arg695Cys	missense_variant	Exon 4 of 4	ENST00000445385.3	NP_997299.2	P0C874
LOC105376105	NR_188610.1 link	n.943-850G>A		intron_variant	Intron 3 of 5
LOC105376105	NR_188611.1 link	n.943-850G>A		intron_variant	Intron 3 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SPATA31D3	ENST00000445385.3 link	c.2083C>T	p.Arg695Cys	missense_variant	Exon 4 of 4	1	NM_207416.3	ENSP00000488117.1	P0C874
ENSG00000267559	ENST00000585776.5 link	n.943-850G>A		intron_variant	Intron 3 of 4	2
ENSG00000267559	ENST00000592744.1 link	n.519-850G>A		intron_variant	Intron 3 of 3	4

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

47898

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00105

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000549

AC:

AN:

54642

Hom.:

AF XY:

0.0000724

AC XY:

AN XY:

27634

show subpopulations

Gnomad AFR exome

AF:

0.000395

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000477

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000477

AC:

AN:

587452

Hom.:

Cov.:

AF XY:

0.0000561

AC XY:

AN XY:

303062

show subpopulations

Gnomad4 AFR exome

AF:

0.000261

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000993

Gnomad4 SAS exome

AF:

0.0000420

Gnomad4 FIN exome

AF:

0.0000306

Gnomad4 NFE exome

AF:

0.0000458

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000209

AC:

AN:

47898

Hom.:

Cov.:

AF XY:

0.0000458

AC XY:

AN XY:

21848

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00105

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 18, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2083C>T (p.R695C) alteration is located in exon 4 (coding exon 4) of the SPATA31D3 gene. This alteration results from a C to T substitution at nucleotide position 2083, causing the arginine (R) at amino acid position 695 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_noAF

Benign

-0.84

CADD

Benign

DANN

Benign

0.73

DEOGEN2

Benign

0.026

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.56

MetaRNN

Benign

0.023

MutationAssessor

Benign

1.0

PrimateAI

Uncertain

0.59

Sift4G

Uncertain

0.0020

Polyphen

0.0040

Vest4

0.16

GERP RS

1.1

Varity_R

0.16

gMVP

0.028

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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