9-42183814-C-T

Variant names:

• chr9-42183814-C-T
• rs748612956
• NM_001145196.1:c.127C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001145196.1(SPATA31A6):​c.127C>T​(p.Leu43Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000286 in 1,398,306 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000029 (1 hom.)
• Consequence: SPATA31A6 NM_001145196.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.262

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11095923).
• BP6: Variant 9-42183814-C-T is Benign according to our data. Variant chr9-42183814-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3321919.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA31A6	NM_001145196.1	c.127C>T	p.Leu43Phe	missense_variant	Exon 1 of 4	ENST00000332857.7	NP_001138668.1
SPATA31A6	XM_011517871.4	c.127C>T	p.Leu43Phe	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.127C>T	p.Leu43Phe	missense_variant	Exon 1 of 4	1	NM_001145196.1	ENSP00000329825.6

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000286 AC: 4 AN: 1398306 Hom.: 1 Cov.: 34 AF XY: 0.00000287 AC XY: 2 AN XY: 695866

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000269

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000279

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 20, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.15
DEOGEN2	Benign	0.0086	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0077	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.00090	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.79	N
Sift	Benign	0.20	T
Sift4G	Uncertain	0.026	D
Vest4		0.36
MutPred		0.27		Loss of catalytic residue at L43 (P = 0.0059);
MVP		0.040
ClinPred		0.15	T
GERP RS		0.81
Varity_R		0.036
gMVP		0.043

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs748612956; hg19: chr9-40700446;