NM_001145196.1:c.117C>A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001145196.1(SPATA31A6):​c.117C>A​(p.Phe39Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000521 in 1,534,714 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000015 ( 0 hom., cov: 23)
Exomes 𝑓: 0.0000043 ( 2 hom. )

Consequence

SPATA31A6
NM_001145196.1 missense

Scores

2
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0330
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 Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.3124007).
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SPATA31A6NM_001145196.1 linkc.117C>A p.Phe39Leu missense_variant Exon 1 of 4 ENST00000332857.7 NP_001138668.1 Q5VVP1
SPATA31A6XM_011517871.4 linkc.117C>A p.Phe39Leu 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.117C>A p.Phe39Leu missense_variant Exon 1 of 4 1 NM_001145196.1 ENSP00000329825.6 Q5VVP1

Frequencies

GnomAD3 genomes
AF:
0.0000147
AC:
2
AN:
136080
Hom.:
0
Cov.:
23
show subpopulations
Gnomad AFR
AF:
0.0000599
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:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000429
AC:
6
AN:
1398634
Hom.:
2
Cov.:
34
AF XY:
0.00000718
AC XY:
5
AN XY:
696032
show subpopulations
Gnomad4 AFR exome
AF:
0.0000342
Gnomad4 AMR exome
AF:
0.00
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:
0.00000466
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000147
AC:
2
AN:
136080
Hom.:
0
Cov.:
23
AF XY:
0.0000302
AC XY:
2
AN XY:
66238
show subpopulations
Gnomad4 AFR
AF:
0.0000599
Gnomad4 AMR
AF:
0.00
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:
0.00
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 12, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.117C>A (p.F39L) alteration is located in exon 1 (coding exon 1) of the SPATA31A6 gene. This alteration results from a C to A substitution at nucleotide position 117, causing the phenylalanine (F) at amino acid position 39 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
Uncertain
0.47
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
7.7
DEOGEN2
Benign
0.017
T
Eigen
Benign
-0.65
Eigen_PC
Benign
-0.89
FATHMM_MKL
Benign
0.021
N
LIST_S2
Benign
0.49
T
M_CAP
Benign
0.0021
T
MetaRNN
Benign
0.31
T
MetaSVM
Benign
-0.99
T
PrimateAI
Benign
0.46
T
PROVEAN
Benign
-1.6
N
Sift
Benign
0.51
T
Sift4G
Uncertain
0.032
D
Vest4
0.54
MutPred
0.35
Gain of helix (P = 0.5668);
MVP
0.048
ClinPred
0.53
D
GERP RS
-1.2
Varity_R
0.043
gMVP
0.047

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: rs771269620; hg19: chr9-40700436; API