chr9-42186012-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001145196.1(SPATA31A6):​c.310C>T​(p.Leu104Phe) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 17)

Consequence

SPATA31A6
NM_001145196.1 missense, splice_region

Scores

17
Splicing: ADA: 0.000009669
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.22
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=0.06011659).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SPATA31A6NM_001145196.1 linkc.310C>T p.Leu104Phe missense_variant, splice_region_variant Exon 4 of 4 ENST00000332857.7 NP_001138668.1 Q5VVP1
SPATA31A6XM_011517871.4 linkc.346C>T p.Leu116Phe missense_variant, splice_region_variant Exon 4 of 4 XP_011516173.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SPATA31A6ENST00000332857.7 linkc.310C>T p.Leu104Phe missense_variant, splice_region_variant Exon 4 of 4 1 NM_001145196.1 ENSP00000329825.6 Q5VVP1
SPATA31A6ENST00000496386.1 linkn.161C>T splice_region_variant, non_coding_transcript_exon_variant Exon 3 of 3 5

Frequencies

GnomAD3 genomes
Cov.:
17
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
17

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 21, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.310C>T (p.L104F) alteration is located in exon 4 (coding exon 4) of the SPATA31A6 gene. This alteration results from a C to T substitution at nucleotide position 310, causing the leucine (L) at amino acid position 104 to be replaced by a phenylalanine (F). 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
0.099
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.76
CADD
Benign
0.16
DANN
Benign
0.91
DEOGEN2
Benign
0.0018
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.0035
N
LIST_S2
Benign
0.46
T
M_CAP
Benign
0.0011
T
MetaRNN
Benign
0.060
T
MetaSVM
Benign
-0.99
T
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-0.050
N
Sift
Benign
0.30
T
Sift4G
Benign
0.70
T
Vest4
0.083
MutPred
0.26
Loss of phosphorylation at S103 (P = 0.1792);
MVP
0.030
ClinPred
0.053
T
GERP RS
-2.9
Varity_R
0.091
gMVP
0.041

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.0000097
dbscSNV1_RF
Benign
0.0
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-40702653; API