9-42185736-C-T

Variant names:

• chr9-42185736-C-T
• rs1174262649
• NM_001145196.1:c.289C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001145196.1(SPATA31A6):​c.289C>T​(p.Leu97Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000438 in 1,140,742 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/7 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 0.0000044 (1 hom.)
• Consequence: SPATA31A6 NM_001145196.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.854

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16399667).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA31A6	NM_001145196.1	c.289C>T	p.Leu97Phe	missense_variant	Exon 3 of 4	ENST00000332857.7	NP_001138668.1
SPATA31A6	XM_011517871.4	c.325C>T	p.Leu109Phe	missense_variant	Exon 3 of 4		XP_011516173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA31A6	ENST00000332857.7	c.289C>T	p.Leu97Phe	missense_variant	Exon 3 of 4	1	NM_001145196.1	ENSP00000329825.6
SPATA31A6	ENST00000496386.1	n.140C>T		non_coding_transcript_exon_variant	Exon 2 of 3	5

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome AF: 0.00000438 AC: 5 AN: 1140742 Hom.: 1 Cov.: 32 AF XY: 0.00000350 AC XY: 2 AN XY: 571934

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: 0.00000584

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 20

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 27, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.289C>T (p.L97F) alteration is located in exon 3 (coding exon 3) of the SPATA31A6 gene. This alteration results from a C to T substitution at nucleotide position 289, causing the leucine (L) at amino acid position 97 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	0.18
CADD	Benign	15
DEOGEN2	Benign	0.099	T
LIST_S2	Benign	0.54	T
MetaRNN	Benign	0.16	T
PROVEAN	Benign	-1.6	N
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0030	D
Vest4		0.30
gMVP		0.11

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1174262649; hg19: -;