17-50552097-A-G

Variant names:

• chr17-50552097-A-G
• rs8065903
• NM_022827.4:c.1874A>G

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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
• Publications: 36 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022827.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA20	NM_022827.4	MANE Select	c.1874A>G	p.Lys625Arg	missense	Exon 14 of 17	NP_073738.2
	SPATA20	NM_001258372.2		c.1826A>G	p.Lys609Arg	missense	Exon 13 of 16	NP_001245301.1
	SPATA20	NM_001258373.2		c.1694A>G	p.Lys565Arg	missense	Exon 14 of 17	NP_001245302.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA20	ENST00000006658.11	TSL:1 MANE Select	c.1874A>G	p.Lys625Arg	missense	Exon 14 of 17	ENSP00000006658.6
	SPATA20	ENST00000356488.8	TSL:1	c.1826A>G	p.Lys609Arg	missense	Exon 13 of 16	ENSP00000348878.4
	SPATA20	ENST00000503127.5	TSL:1	n.*1797A>G		non_coding_transcript_exon	Exon 14 of 17	ENSP00000426228.1

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

GnomAD2 exomes AF: 0.788 AC: 196441 AN: 249442 AF XY: 0.778

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 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

African (AFR) AF: 0.954 AC: 31956 AN: 33480

American (AMR) AF: 0.833 AC: 37218 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.858 AC: 22420 AN: 26134

East Asian (EAS) AF: 0.969 AC: 38478 AN: 39692

South Asian (SAS) AF: 0.739 AC: 63719 AN: 86240

European-Finnish (FIN) AF: 0.726 AC: 38561 AN: 53094

Middle Eastern (MID) AF: 0.782 AC: 4513 AN: 5768

European-Non Finnish (NFE) AF: 0.737 AC: 819382 AN: 1111836

Other (OTH) AF: 0.779 AC: 47035 AN: 60376

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

African (AFR) AF: 0.947 AC: 39329 AN: 41550

American (AMR) AF: 0.826 AC: 12641 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.852 AC: 2958 AN: 3472

East Asian (EAS) AF: 0.968 AC: 4998 AN: 5164

South Asian (SAS) AF: 0.731 AC: 3527 AN: 4826

European-Finnish (FIN) AF: 0.713 AC: 7526 AN: 10560

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.733 AC: 49803 AN: 67968

Other (OTH) AF: 0.813 AC: 1718 AN: 2112

Alfa AF: 0.768 Hom.: 175017

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 v4.9

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
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.19	T
MetaRNN	Benign	5.4e-7	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.14	N
PhyloP100		0.33
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.36	N
REVEL	Benign	0.021
Sift	Benign	1.0	T
Sift4G	Benign	0.39	T
Polyphen		0.0	B
Vest4		0.0090
MPC		0.16
ClinPred		0.0018	T
GERP RS		1.6
Varity_R		0.023
gMVP		0.15
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8065903; hg19: chr17-48629458; COSMIC: COSV50066051; COSMIC: COSV50066051;