9-42186012-C-T

Variant names:

• chr9-42186012-C-T
• NM_001145196.1:c.310C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_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: Splicing: ADA: 0.000009669
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.22

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]

ACMG classification

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
SPATA31A6	NM_001145196.1	c.310C>T	p.Leu104Phe	missense_variant, splice_region_variant	Exon 4 of 4	ENST00000332857.7	NP_001138668.1
SPATA31A6	XM_011517871.4	c.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
SPATA31A6	ENST00000332857.7	c.310C>T	p.Leu104Phe	missense_variant, splice_region_variant	Exon 4 of 4	1	NM_001145196.1	ENSP00000329825.6
SPATA31A6	ENST00000496386.1	n.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

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;