9-42183706-C-G

Variant names:

• chr9-42183706-C-G
• rs762811181
• NM_001145196.1:c.19C>G

Variant summary

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

The NM_001145196.1(SPATA31A6):​c.19C>G​(p.Pro7Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000998 in 1,402,448 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.000010 (2 hom.)
• Consequence: SPATA31A6 NM_001145196.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.15

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=0.18001962).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA31A6	NM_001145196.1	c.19C>G	p.Pro7Ala	missense_variant	Exon 1 of 4	ENST00000332857.7	NP_001138668.1
SPATA31A6	XM_011517871.4	c.19C>G	p.Pro7Ala	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.19C>G	p.Pro7Ala	missense_variant	Exon 1 of 4	1	NM_001145196.1	ENSP00000329825.6

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000998 AC: 14 AN: 1402448 Hom.: 2 Cov.: 34 AF XY: 0.0000100 AC XY: 7 AN XY: 697838

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: 0.0000112

Gnomad4 OTH exome AF: 0.0000347

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.19C>G (p.P7A) alteration is located in exon 1 (coding exon 1) of the SPATA31A6 gene. This alteration results from a C to G substitution at nucleotide position 19, causing the proline (P) at amino acid position 7 to be replaced by an alanine (A). 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	0.13
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	1.7
DANN	Benign	0.96
DEOGEN2	Benign	0.0081	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.0076	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.98	T
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-2.3	N
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.048	D
Vest4		0.41
MutPred		0.47		Gain of helix (P = 6e-04);
MVP		0.055
ClinPred		0.58	D
GERP RS		1.4
Varity_R		0.054
gMVP		0.055

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: rs762811181; hg19: chr9-40700338;