9-61191465-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_015667.2(SPATA31A7):​c.202C>T​(p.Arg68Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00013 in 1,272,846 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. 7/9 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R68Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00018 ( 6 hom., cov: 17)
Exomes 𝑓: 0.00013 ( 46 hom. )
Failed GnomAD Quality Control

Consequence

SPATA31A7
NM_015667.2 missense

Scores

7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.690
Variant links:
Genes affected
SPATA31A7 (HGNC:32007): (SPATA31 subfamily A member 7) 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 -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.09756231).
BS2
High Homozygotes in GnomAdExome4 at 46 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SPATA31A7NM_015667.2 linkc.202C>T p.Arg68Trp missense_variant Exon 2 of 4 ENST00000619167.2 NP_056482.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SPATA31A7ENST00000619167.2 linkc.202C>T p.Arg68Trp missense_variant Exon 2 of 4 1 NM_015667.2 ENSP00000484807.1 Q8IWB4

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
21
AN:
116286
Hom.:
6
Cov.:
17
FAILED QC
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000884
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:
0.000351
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000553
AC:
13
AN:
235194
Hom.:
3
AF XY:
0.0000391
AC XY:
5
AN XY:
127848
show subpopulations
Gnomad AFR exome
AF:
0.000886
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:
0.0000486
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000130
AC:
166
AN:
1272846
Hom.:
46
Cov.:
30
AF XY:
0.000160
AC XY:
101
AN XY:
631634
show subpopulations
Gnomad4 AFR exome
AF:
0.0000800
Gnomad4 AMR exome
AF:
0.0000528
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000310
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000155
Gnomad4 OTH exome
AF:
0.0000969
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.000181
AC:
21
AN:
116286
Hom.:
6
Cov.:
17
AF XY:
0.000160
AC XY:
9
AN XY:
56234
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000884
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000351
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000843
Hom.:
0

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 19, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.202C>T (p.R68W) alteration is located in exon 2 (coding exon 2) of the SPATA31A7 gene. This alteration results from a C to T substitution at nucleotide position 202, causing the arginine (R) at amino acid position 68 to be replaced by a tryptophan (W). 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
0.11
BayesDel_noAF
Benign
-0.98
CADD
Benign
9.1
DANN
Benign
0.72
DEOGEN2
Benign
0.027
T
LIST_S2
Benign
0.50
T
MetaRNN
Benign
0.098
T
Sift4G
Benign
0.094
T
Vest4
0.22
gMVP
0.20

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: rs374438064; hg19: chr9-65508181; API