chr9-81932657-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001145197.1(SPATA31D4):​c.2496C>A​(p.Ser832Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00047 ( 1 hom., cov: 20)
Exomes 𝑓: 0.000047 ( 1 hom. )
Failed GnomAD Quality Control

Consequence

SPATA31D4
NM_001145197.1 missense

Scores

1
3
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0660
Variant links:
Genes affected
SPATA31D4 (HGNC:38601): (SPATA31 subfamily D member 4) 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 -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.15085861).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SPATA31D4NM_001145197.1 linkc.2496C>A p.Ser832Arg missense_variant Exon 4 of 4 ENST00000419782.5 NP_001138669.1 Q6ZUB0
LOC105376105NR_188610.1 linkn.1040-1263G>T intron_variant Intron 4 of 5
LOC105376105NR_188611.1 linkn.1229-1263G>T intron_variant Intron 4 of 5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SPATA31D4ENST00000419782.5 linkc.2496C>A p.Ser832Arg missense_variant Exon 4 of 4 1 NM_001145197.1 ENSP00000488251.1 Q6ZUB0
ENSG00000267559ENST00000585776.5 linkn.1040-1263G>T intron_variant Intron 4 of 4 2

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
59
AN:
132924
Hom.:
0
Cov.:
20
FAILED QC
Gnomad AFR
AF:
0.00151
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000227
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:
0.00
Gnomad OTH
AF:
0.00112
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000475
AC:
66
AN:
1390266
Hom.:
1
Cov.:
30
AF XY:
0.0000448
AC XY:
31
AN XY:
691290
show subpopulations
Gnomad4 AFR exome
AF:
0.00161
Gnomad4 AMR exome
AF:
0.0000475
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000285
Gnomad4 OTH exome
AF:
0.000156
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.000466
AC:
62
AN:
133024
Hom.:
1
Cov.:
20
AF XY:
0.000403
AC XY:
26
AN XY:
64476
show subpopulations
Gnomad4 AFR
AF:
0.00159
Gnomad4 AMR
AF:
0.000227
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00111
Alfa
AF:
0.000759
Hom.:
0
ExAC
AF:
0.0000265
AC:
3

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 05, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2496C>A (p.S832R) alteration is located in exon 4 (coding exon 4) of the SPATA31D4 gene. This alteration results from a C to A substitution at nucleotide position 2496, causing the serine (S) at amino acid position 832 to be replaced by an arginine (R). 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
Uncertain
0.37
BayesDel_noAF
Benign
-0.94
CADD
Benign
13
DANN
Benign
0.68
DEOGEN2
Benign
0.020
T
FATHMM_MKL
Benign
0.0033
N
LIST_S2
Benign
0.72
T
MetaRNN
Benign
0.15
T
MutationAssessor
Pathogenic
3.1
M
PrimateAI
Uncertain
0.52
T
Sift4G
Uncertain
0.011
D
Polyphen
1.0
D
Vest4
0.32
GERP RS
-0.29
Varity_R
0.069
gMVP
0.077

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.

Other links and lift over

dbSNP: rs781376500; hg19: chr9-84547572; API