rs10974657

chr9-4622453-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001353486.2(SPATA6L):c.727A>G(p.Arg243Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0628 in 1,613,362 control chromosomes in the GnomAD database, including 5,095 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.070 (523 hom., cov: 32)
  • Exomes 𝑓: 0.062 (4572 hom.)
• Consequence: SPATA6L NM_001353486.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.969

Genes affected

SPATA6L (HGNC:25472): (spermatogenesis associated 6 like) Predicted to enable myosin light chain binding activity. Predicted to be involved in spermatogenesis. Predicted to be located in sperm connecting piece. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0013862252).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPATA6L	NM_001353486.2	c.727A>G	p.Arg243Gly	missense_variant	7/12	ENST00000682582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPATA6L	ENST00000682582.1	c.727A>G	p.Arg243Gly	missense_variant	7/12		NM_001353486.2

Frequencies

GnomAD3 genomes AF: 0.0704 AC: 10716 AN: 152172 Hom.: 522 Cov.: 32

Gnomad AFR AF: 0.0642

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.0968

Gnomad ASJ AF: 0.0550

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.0692

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0517

Gnomad OTH AF: 0.0594

GnomAD3 exomes AF: 0.0828 AC: 20622 AN: 249146 Hom.: 1254 AF XY: 0.0815 AC XY: 11025 AN XY: 135194

Gnomad AFR exome AF: 0.0631

Gnomad AMR exome AF: 0.0997

Gnomad ASJ exome AF: 0.0615

Gnomad EAS exome AF: 0.265

Gnomad SAS exome AF: 0.105

Gnomad FIN exome AF: 0.0654

Gnomad NFE exome AF: 0.0515

Gnomad OTH exome AF: 0.0679

GnomAD4 exome AF: 0.0620 AC: 90614 AN: 1461072 Hom.: 4572 Cov.: 30 AF XY: 0.0627 AC XY: 45594 AN XY: 726890

Gnomad4 AFR exome AF: 0.0630

Gnomad4 AMR exome AF: 0.0985

Gnomad4 ASJ exome AF: 0.0623

Gnomad4 EAS exome AF: 0.314

Gnomad4 SAS exome AF: 0.101

Gnomad4 FIN exome AF: 0.0683

Gnomad4 NFE exome AF: 0.0477

Gnomad4 OTH exome AF: 0.0705

GnomAD4 genome AF: 0.0704 AC: 10728 AN: 152290 Hom.: 523 Cov.: 32 AF XY: 0.0744 AC XY: 5538 AN XY: 74460

Gnomad4 AFR AF: 0.0644

Gnomad4 AMR AF: 0.0965

Gnomad4 ASJ AF: 0.0550

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.0692

Gnomad4 NFE AF: 0.0517

Gnomad4 OTH AF: 0.0630

Alfa AF: 0.0590 Hom.: 1016

Bravo AF: 0.0718

TwinsUK AF: 0.0442 AC: 164

ALSPAC AF: 0.0436 AC: 168

ESP6500AA AF: 0.0694 AC: 258

ESP6500EA AF: 0.0488 AC: 400

ExAC AF: 0.0815 AC: 9841

Asia WGS AF: 0.197 AC: 685 AN: 3478

EpiCase AF: 0.0502

EpiControl AF: 0.0458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.48
Cadd	Benign	21
Dann	Uncertain	0.99
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.80	T;T
MetaRNN	Benign	0.0014	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.78	P;P;P;P
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.038
Sift	Benign	0.033	D;T
Sift4G	Uncertain	0.049	D;D
Vest4		0.26
MPC		0.0018
ClinPred		0.017	T
GERP RS		1.4
gMVP		0.10

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: rs10974657; hg19: chr9-4622453; COSMIC: COSV56304698; COSMIC: COSV56304698;