9-42183706-C-T

Variant names:

• chr9-42183706-C-T
• rs762811181
• NM_001145196.1:c.19C>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.19C>T​(p.Pro7Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000293 in 1,535,408 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P7A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000015 (0 hom., cov: 23)
  • Exomes 𝑓: 0.000031 (5 hom.)
• Consequence: SPATA31A6 NM_001145196.1 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.10807362).
• BS2: High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA31A6	NM_001145196.1	c.19C>T	p.Pro7Ser	missense_variant	Exon 1 of 4	ENST00000332857.7	NP_001138668.1
SPATA31A6	XM_011517871.4	c.19C>T	p.Pro7Ser	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>T	p.Pro7Ser	missense_variant	Exon 1 of 4	1	NM_001145196.1	ENSP00000329825.6

Frequencies

GnomAD3 genomes AF: 0.0000150 AC: 2 AN: 132962 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

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: 0.0000317

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000307 AC: 43 AN: 1402446 Hom.: 5 Cov.: 34 AF XY: 0.0000358 AC XY: 25 AN XY: 697836

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: 0.0000372

Gnomad4 OTH exome AF: 0.0000520

GnomAD4 genome AF: 0.0000150 AC: 2 AN: 132962 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 64648

Gnomad4 AFR AF: 0.00

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: 0.0000317

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000977 Hom.: 1

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	1.4
DANN	Benign	0.96
DEOGEN2	Benign	0.0063	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.00070	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.95	T
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-2.1	N
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.60	T
Vest4		0.34
MutPred		0.45		Loss of loop (P = 0.0288);
MVP		0.030
ClinPred		0.23	T
GERP RS		1.4
Varity_R		0.045
gMVP		0.096

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;