9-42183755-C-A

Variant names:

• chr9-42183755-C-A
• rs1365383309
• NM_001145196.1:c.68C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001145196.1(SPATA31A6):​c.68C>A​(p.Pro23Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,401,300 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 7/10 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: 0.0000021 (0 hom.)
• Consequence: SPATA31A6 NM_001145196.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0480

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3318274).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA31A6	NM_001145196.1	c.68C>A	p.Pro23Gln	missense_variant	Exon 1 of 4	ENST00000332857.7	NP_001138668.1
SPATA31A6	XM_011517871.4	c.68C>A	p.Pro23Gln	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.68C>A	p.Pro23Gln	missense_variant	Exon 1 of 4	1	NM_001145196.1	ENSP00000329825.6

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000214 AC: 3 AN: 1401300 Hom.: 0 Cov.: 34 AF XY: 0.00000143 AC XY: 1 AN XY: 697416

Gnomad4 AFR exome AF: 0.0000341

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: 0.00

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

Oct 27, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.68C>A (p.P23Q) alteration is located in exon 1 (coding exon 1) of the SPATA31A6 gene. This alteration results from a C to A substitution at nucleotide position 68, causing the proline (P) at amino acid position 23 to be replaced by a glutamine (Q). 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	0.17
BayesDel_noAF	Benign	-0.89
CADD	Benign	17
DANN	Benign	0.94
DEOGEN2	Benign	0.020	T
LIST_S2	Benign	0.45	T
MetaRNN	Benign	0.33	T
PROVEAN	Benign	-1.5	N
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.032	D
Vest4		0.49
gMVP		0.084

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1365383309; hg19: chr9-43630634;