chr9-42183860-C-G

Variant names:

• chr9-42183860-C-G
• rs760232948
• NM_001145196.1:c.173C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001145196.1(SPATA31A6):​c.173C>G​(p.Ser58Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000717 in 1,395,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/16 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. S58L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: SPATA31A6 NM_001145196.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.969
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1918799).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145196.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA31A6	NM_001145196.1	MANE Select	c.173C>G	p.Ser58Trp	missense	Exon 1 of 4	NP_001138668.1	Q5VVP1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA31A6	ENST00000332857.7	TSL:1 MANE Select	c.173C>G	p.Ser58Trp	missense	Exon 1 of 4	ENSP00000329825.6	Q5VVP1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 7.17e-7 AC: 1 AN: 1395654 Hom.: 0 Cov.: 34 AF XY: 0.00000144 AC XY: 1 AN XY: 694556

African (AFR) AF: 0.00 AC: 0 AN: 29238

American (AMR) AF: 0.00 AC: 0 AN: 42776

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24604

East Asian (EAS) AF: 0.00 AC: 0 AN: 37232

South Asian (SAS) AF: 0.00 AC: 0 AN: 82442

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3960

European-Non Finnish (NFE) AF: 9.32e-7 AC: 1 AN: 1073400

Other (OTH) AF: 0.00 AC: 0 AN: 57472

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.0081	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.97
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.3	N
Sift	Benign	0.074	T
Sift4G	Benign	0.062	T
Vest4		0.40
MutPred		0.22		Loss of glycosylation at S58 (P = 0.0164)
MVP		0.30
ClinPred		0.51	D
GERP RS		0.63
PromoterAI		-0.0010	Neutral
gMVP		0.081

Splicing

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

Other links and lift over

dbSNP: rs760232948; hg19: chr9-40700492;