9-42183814-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001145196.1(SPATA31A6):​c.127C>T​(p.Leu43Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000286 in 1,398,306 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 24)
Exomes 𝑓: 0.0000029 ( 1 hom. )

Consequence

SPATA31A6
NM_001145196.1 missense

Scores

1
15

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.262
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.11095923).
BP6
Variant 9-42183814-C-T is Benign according to our data. Variant chr9-42183814-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3321919.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SPATA31A6NM_001145196.1 linkc.127C>T p.Leu43Phe missense_variant Exon 1 of 4 ENST00000332857.7 NP_001138668.1 Q5VVP1
SPATA31A6XM_011517871.4 linkc.127C>T p.Leu43Phe 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.127C>T p.Leu43Phe missense_variant Exon 1 of 4 1 NM_001145196.1 ENSP00000329825.6 Q5VVP1

Frequencies

GnomAD3 genomes
Cov.:
24
GnomAD4 exome
AF:
0.00000286
AC:
4
AN:
1398306
Hom.:
1
Cov.:
34
AF XY:
0.00000287
AC XY:
2
AN XY:
695866
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000269
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000279
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
24

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Mar 20, 2024
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.082
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.66
CADD
Benign
0.15
DEOGEN2
Benign
0.0086
T
Eigen
Benign
-0.90
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.0077
N
LIST_S2
Benign
0.44
T
M_CAP
Benign
0.00090
T
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-0.79
N
Sift
Benign
0.20
T
Sift4G
Uncertain
0.026
D
Vest4
0.36
MutPred
0.27
Loss of catalytic residue at L43 (P = 0.0059);
MVP
0.040
ClinPred
0.15
T
GERP RS
0.81
Varity_R
0.036
gMVP
0.043

Splicing

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: rs748612956; hg19: chr9-40700446; API