chr9-81947336-C-T

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

2
8

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]

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
SPATA31D3NM_207416.3 linkc.2083C>T p.Arg695Cys missense_variant Exon 4 of 4 ENST00000445385.3 NP_997299.2 P0C874
LOC105376105NR_188610.1 linkn.943-850G>A intron_variant Intron 3 of 5
LOC105376105NR_188611.1 linkn.943-850G>A intron_variant Intron 3 of 5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SPATA31D3ENST00000445385.3 linkc.2083C>T p.Arg695Cys missense_variant Exon 4 of 4 1 NM_207416.3 ENSP00000488117.1 P0C874
ENSG00000267559ENST00000585776.5 linkn.943-850G>A intron_variant Intron 3 of 4 2
ENSG00000267559ENST00000592744.1 linkn.519-850G>A intron_variant Intron 3 of 3 4

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
1
AN:
47898
Hom.:
0
Cov.:
6
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:
3
AN:
54642
Hom.:
0
AF XY:
0.0000724
AC XY:
2
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:
28
AN:
587452
Hom.:
0
Cov.:
8
AF XY:
0.0000561
AC XY:
17
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:
1
AN:
47898
Hom.:
0
Cov.:
6
AF XY:
0.0000458
AC XY:
1
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
15
DANN
Benign
0.73
DEOGEN2
Benign
0.026
T
FATHMM_MKL
Benign
0.013
N
LIST_S2
Benign
0.56
T
MetaRNN
Benign
0.023
T
MutationAssessor
Benign
1.0
L
PrimateAI
Uncertain
0.59
T
Sift4G
Uncertain
0.0020
D
Polyphen
0.0040
B
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.

Other links and lift over

dbSNP: rs1281326580; hg19: chr9-84562251; API