rs10974657

Variant names:

• chr9-4622453-T-C
• rs10974657
• NM_001353486.2:c.727A>G

Variant summary

Our verdict is Benign. The variant received -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. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SPATA6L	NM_001353486.2	c.727A>G	p.Arg243Gly	missense_variant	Exon 7 of 12	ENST00000682582.1	NP_001340415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA6L	ENST00000682582.1	c.727A>G	p.Arg243Gly	missense_variant	Exon 7 of 12		NM_001353486.2	ENSP00000506787.1

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

GnomAD2 exomes AF: 0.0828 AC: 20622 AN: 249146 AF XY: 0.0815

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 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

African (AFR) AF: 0.0630 AC: 2107 AN: 33462

American (AMR) AF: 0.0985 AC: 4402 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.0623 AC: 1628 AN: 26126

East Asian (EAS) AF: 0.314 AC: 12445 AN: 39672

South Asian (SAS) AF: 0.101 AC: 8694 AN: 86180

European-Finnish (FIN) AF: 0.0683 AC: 3638 AN: 53238

Middle Eastern (MID) AF: 0.0774 AC: 446 AN: 5762

European-Non Finnish (NFE) AF: 0.0477 AC: 52998 AN: 1111546

Other (OTH) AF: 0.0705 AC: 4256 AN: 60380

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

African (AFR) AF: 0.0644 AC: 2677 AN: 41582

American (AMR) AF: 0.0965 AC: 1476 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0550 AC: 191 AN: 3472

East Asian (EAS) AF: 0.262 AC: 1358 AN: 5178

South Asian (SAS) AF: 0.115 AC: 554 AN: 4826

European-Finnish (FIN) AF: 0.0692 AC: 734 AN: 10614

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0517 AC: 3515 AN: 68012

Other (OTH) AF: 0.0630 AC: 133 AN: 2110

Alfa AF: 0.0602 Hom.: 1552

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
PhyloP100		0.97
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
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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