9-42183778-A-T

Variant names:

• chr9-42183778-A-T
• rs1829390085
• NM_001145196.1:c.91A>T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001145196.1(SPATA31A6):​c.91A>T​(p.Thr31Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000786 in 1,400,202 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/11 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. T31I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000079 (3 hom.)
• Consequence: SPATA31A6 NM_001145196.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0400

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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14525259).
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA31A6	NM_001145196.1	c.91A>T	p.Thr31Ser	missense_variant	Exon 1 of 4	ENST00000332857.7	NP_001138668.1
SPATA31A6	XM_011517871.4	c.91A>T	p.Thr31Ser	missense_variant	Exon 1 of 4		XP_011516173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA31A6	ENST00000332857.7	c.91A>T	p.Thr31Ser	missense_variant	Exon 1 of 4	1	NM_001145196.1	ENSP00000329825.6

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000786 AC: 11 AN: 1400202 Hom.: 3 Cov.: 34 AF XY: 0.0000115 AC XY: 8 AN XY: 696828

Gnomad4 AFR exome AF: 0.00

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: 0.00000838

Gnomad4 OTH exome AF: 0.0000347

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 16, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.91A>T (p.T31S) alteration is located in exon 1 (coding exon 1) of the SPATA31A6 gene. This alteration results from a A to T substitution at nucleotide position 91, causing the threonine (T) at amino acid position 31 to be replaced by a serine (S). 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	0.19
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.7
DANN	Benign	0.71
DEOGEN2	Benign	0.081	T
LIST_S2	Benign	0.38	T
MetaRNN	Benign	0.15	T
PROVEAN	Benign	-0.76	N
Sift	Benign	0.037	D
Sift4G	Benign	0.46	T
Vest4		0.38
gMVP		0.050

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

Other links and lift over

dbSNP: rs1829390085; hg19: chr9-43630611;