9-42183860-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001145196.1(SPATA31A6):​c.173C>T​(p.Ser58Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 1,531,920 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000022 ( 0 hom., cov: 24)
Exomes 𝑓: 0.000014 ( 3 hom. )

Consequence

SPATA31A6
NM_001145196.1 missense

Scores

17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.969
Variant links:
Genes affected
SPATA31A6 (HGNC:32006): (SPATA31 subfamily A member 6) Predicted to enable actin binding activity. Predicted to be involved in cell differentiation and spermatogenesis. Predicted to be located in acrosomal vesicle. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.051556468).
BS2
High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SPATA31A6NM_001145196.1 linkc.173C>T p.Ser58Leu missense_variant Exon 1 of 4 ENST00000332857.7 NP_001138668.1 Q5VVP1
SPATA31A6XM_011517871.4 linkc.173C>T p.Ser58Leu missense_variant Exon 1 of 4 XP_011516173.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SPATA31A6ENST00000332857.7 linkc.173C>T p.Ser58Leu missense_variant Exon 1 of 4 1 NM_001145196.1 ENSP00000329825.6 Q5VVP1

Frequencies

GnomAD3 genomes
AF:
0.0000220
AC:
3
AN:
136266
Hom.:
0
Cov.:
24
show subpopulations
Gnomad AFR
AF:
0.0000299
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:
0.000102
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000155
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000143
AC:
20
AN:
1395654
Hom.:
3
Cov.:
34
AF XY:
0.0000158
AC XY:
11
AN XY:
694556
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000468
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000728
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000112
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000220
AC:
3
AN:
136266
Hom.:
0
Cov.:
24
AF XY:
0.0000452
AC XY:
3
AN XY:
66348
show subpopulations
Gnomad4 AFR
AF:
0.0000299
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000102
Gnomad4 NFE
AF:
0.0000155
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000113

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 26, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.173C>T (p.S58L) alteration is located in exon 1 (coding exon 1) of the SPATA31A6 gene. This alteration results from a C to T substitution at nucleotide position 173, causing the serine (S) at amino acid position 58 to be replaced by a leucine (L). 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
0.083
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
7.5
DANN
Benign
0.85
DEOGEN2
Benign
0.0019
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.026
N
LIST_S2
Benign
0.52
T
M_CAP
Benign
0.0017
T
MetaRNN
Benign
0.052
T
MetaSVM
Benign
-0.96
T
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-0.65
N
Sift
Benign
0.42
T
Sift4G
Benign
0.45
T
Vest4
0.18
MutPred
0.18
Loss of glycosylation at S58 (P = 0.0164);
MVP
0.088
ClinPred
0.12
T
GERP RS
0.63
Varity_R
0.053
gMVP
0.078

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: rs760232948; hg19: chr9-40700492; COSMIC: COSV60534893; COSMIC: COSV60534893; API