rs8076632

Positions:

• chr17-50548567-C-G

Variant summary

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

The ENST00000006658.11(SPATA20):​c.310C>G​(p.Gln104Glu) variant causes a missense change. The variant allele was found at a frequency of 0.359 in 1,611,484 control chromosomes in the GnomAD database, including 110,899 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 0.42 (15029 hom., cov: 32)
  • Exomes 𝑓: 0.35 (95870 hom.)
• Consequence: SPATA20 ENST00000006658.11 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.36

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=8.233564E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATA20	NM_022827.4	c.310C>G	p.Gln104Glu	missense_variant	4/17	ENST00000006658.11	NP_073738.2
SPATA20	NM_001258372.2	c.262C>G	p.Gln88Glu	missense_variant	3/16		NP_001245301.1
SPATA20	NM_001258373.2	c.130C>G	p.Gln44Glu	missense_variant	4/17		NP_001245302.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPATA20	ENST00000006658.11	c.310C>G	p.Gln104Glu	missense_variant	4/17	1	NM_022827.4	ENSP00000006658

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63497 AN: 151896 Hom.: 15013 Cov.: 32

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.0734

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.396

GnomAD3 exomes AF: 0.321 AC: 79293 AN: 247362 Hom.: 14660 AF XY: 0.314 AC XY: 42122 AN XY: 133946

Gnomad AFR exome AF: 0.644

Gnomad AMR exome AF: 0.239

Gnomad ASJ exome AF: 0.439

Gnomad EAS exome AF: 0.0676

Gnomad SAS exome AF: 0.199

Gnomad FIN exome AF: 0.327

Gnomad NFE exome AF: 0.362

Gnomad OTH exome AF: 0.335

GnomAD4 exome AF: 0.352 AC: 514334 AN: 1459470 Hom.: 95870 Cov.: 52 AF XY: 0.347 AC XY: 252161 AN XY: 725904

Gnomad4 AFR exome AF: 0.656

Gnomad4 AMR exome AF: 0.248

Gnomad4 ASJ exome AF: 0.434

Gnomad4 EAS exome AF: 0.0763

Gnomad4 SAS exome AF: 0.205

Gnomad4 FIN exome AF: 0.332

Gnomad4 NFE exome AF: 0.367

Gnomad4 OTH exome AF: 0.361

GnomAD4 genome AF: 0.418 AC: 63547 AN: 152014 Hom.: 15029 Cov.: 32 AF XY: 0.410 AC XY: 30472 AN XY: 74294

Gnomad4 AFR AF: 0.643

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.425

Gnomad4 EAS AF: 0.0735

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.358

Gnomad4 OTH AF: 0.391

Alfa AF: 0.382 Hom.: 3587

Bravo AF: 0.431

TwinsUK AF: 0.361 AC: 1339

ALSPAC AF: 0.364 AC: 1404

ESP6500AA AF: 0.635 AC: 2797

ESP6500EA AF: 0.361 AC: 3108

ExAC AF: 0.329 AC: 39911

Asia WGS AF: 0.175 AC: 610 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	20
DANN	Benign	0.89
DEOGEN2	Benign	0.033	.;.;T;T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.20
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.81	T;T;T;T
MetaRNN	Benign	0.0000082	T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.55	.;.;N;.
MutationTaster	Benign	0.000096	P;P;P
PrimateAI	Benign	0.46	T
PROVEAN	Benign	0.53	.;N;N;.
REVEL	Benign	0.069
Sift	Benign	0.74	.;T;T;.
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0030, 0.0090	.;B;B;.
Vest4		0.18
MPC		0.22
ClinPred		0.024	T
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.28

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: rs8076632; hg19: chr17-48625928; COSMIC: COSV50066559; COSMIC: COSV50066559;