rs8065903

Positions:

• chr17-50552097-A-G
• chr17-50552097-A-T

Variant summary

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

The NM_022827.4(SPATA20):​c.1874A>G​(p.Lys625Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 1,613,474 control chromosomes in the GnomAD database, including 470,047 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.81 (50849 hom., cov: 32)
  • Exomes 𝑓: 0.75 (419198 hom.)
• Consequence: SPATA20 NM_022827.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.325

Genes affected

SPATA20 (HGNC:26125): (spermatogenesis associated 20) Predicted to be involved in carbohydrate metabolic process; cell differentiation; and spermatogenesis. Predicted to be located in extracellular region. [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=5.4388806E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATA20	NM_022827.4	c.1874A>G	p.Lys625Arg	missense_variant	14/17	ENST00000006658.11	NP_073738.2
SPATA20	NM_001258372.2	c.1826A>G	p.Lys609Arg	missense_variant	13/16		NP_001245301.1
SPATA20	NM_001258373.2	c.1694A>G	p.Lys565Arg	missense_variant	14/17		NP_001245302.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPATA20	ENST00000006658.11	c.1874A>G	p.Lys625Arg	missense_variant	14/17	1	NM_022827.4	ENSP00000006658

Frequencies

GnomAD3 genomes AF: 0.811 AC: 123315 AN: 152042 Hom.: 50788 Cov.: 32

Gnomad AFR AF: 0.947

Gnomad AMI AF: 0.792

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.852

Gnomad EAS AF: 0.968

Gnomad SAS AF: 0.732

Gnomad FIN AF: 0.713

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.733

Gnomad OTH AF: 0.812

GnomAD3 exomes AF: 0.788 AC: 196441 AN: 249442 Hom.: 78242 AF XY: 0.778 AC XY: 105286 AN XY: 135342

Gnomad AFR exome AF: 0.952

Gnomad AMR exome AF: 0.837

Gnomad ASJ exome AF: 0.861

Gnomad EAS exome AF: 0.967

Gnomad SAS exome AF: 0.740

Gnomad FIN exome AF: 0.725

Gnomad NFE exome AF: 0.738

Gnomad OTH exome AF: 0.778

GnomAD4 exome AF: 0.755 AC: 1103282 AN: 1461314 Hom.: 419198 Cov.: 59 AF XY: 0.753 AC XY: 547217 AN XY: 726954

Gnomad4 AFR exome AF: 0.954

Gnomad4 AMR exome AF: 0.833

Gnomad4 ASJ exome AF: 0.858

Gnomad4 EAS exome AF: 0.969

Gnomad4 SAS exome AF: 0.739

Gnomad4 FIN exome AF: 0.726

Gnomad4 NFE exome AF: 0.737

Gnomad4 OTH exome AF: 0.779

GnomAD4 genome AF: 0.811 AC: 123434 AN: 152160 Hom.: 50849 Cov.: 32 AF XY: 0.810 AC XY: 60278 AN XY: 74378

Gnomad4 AFR AF: 0.947

Gnomad4 AMR AF: 0.826

Gnomad4 ASJ AF: 0.852

Gnomad4 EAS AF: 0.968

Gnomad4 SAS AF: 0.731

Gnomad4 FIN AF: 0.713

Gnomad4 NFE AF: 0.733

Gnomad4 OTH AF: 0.813

Alfa AF: 0.760 Hom.: 80055

Bravo AF: 0.830

TwinsUK AF: 0.734 AC: 2721

ALSPAC AF: 0.751 AC: 2895

ESP6500AA AF: 0.947 AC: 4173

ESP6500EA AF: 0.742 AC: 6383

ExAC AF: 0.785 AC: 95029

Asia WGS AF: 0.870 AC: 3024 AN: 3478

EpiCase AF: 0.746

EpiControl AF: 0.740

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	14
DANN	Benign	0.73
DEOGEN2	Benign	0.056	.;.;T;T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.19	T;T;T;T
MetaRNN	Benign	5.4e-7	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.14	.;.;N;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.36	.;N;N;.
REVEL	Benign	0.021
Sift	Benign	1.0	.;T;T;.
Sift4G	Benign	0.39	T;T;T;T
Polyphen		0.0	.;B;B;.
Vest4		0.0090
MPC		0.16
ClinPred		0.0018	T
GERP RS		1.6
Varity_R		0.023
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs8065903; hg19: chr17-48629458; COSMIC: COSV50066051; COSMIC: COSV50066051;