NM_022827.4:c.1495T>A

Variant names:

• chr17-50551109-T-A
• rs9913430
• NM_022827.4:c.1495T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022827.4(SPATA20):​c.1495T>A​(p.Ser499Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 1,612,064 control chromosomes in the GnomAD database, including 75,652 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 0.39 (14902 hom., cov: 33)
  • Exomes 𝑓: 0.27 (60750 hom.)
• Consequence: SPATA20 NM_022827.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.106
• Publications: 41 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=3.3013168E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.693 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA20	NM_022827.4	MANE Select	c.1495T>A	p.Ser499Thr	missense	Exon 12 of 17	NP_073738.2
	SPATA20	NM_001258372.2		c.1447T>A	p.Ser483Thr	missense	Exon 11 of 16	NP_001245301.1	Q8TB22-1
	SPATA20	NM_001258373.2		c.1315T>A	p.Ser439Thr	missense	Exon 12 of 17	NP_001245302.1	Q8TB22-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA20	ENST00000006658.11	TSL:1 MANE Select	c.1495T>A	p.Ser499Thr	missense	Exon 12 of 17	ENSP00000006658.6	Q8TB22-2
	SPATA20	ENST00000356488.8	TSL:1	c.1447T>A	p.Ser483Thr	missense	Exon 11 of 16	ENSP00000348878.4	Q8TB22-1
	SPATA20	ENST00000503127.5	TSL:1	n.*1418T>A		non_coding_transcript_exon	Exon 12 of 17	ENSP00000426228.1	D6R947

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59944 AN: 152006 Hom.: 14853 Cov.: 33

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.388

GnomAD2 exomes AF: 0.304 AC: 75382 AN: 248364 AF XY: 0.288

Gnomad AFR exome AF: 0.705

Gnomad AMR exome AF: 0.421

Gnomad ASJ exome AF: 0.447

Gnomad EAS exome AF: 0.0974

Gnomad FIN exome AF: 0.260

Gnomad NFE exome AF: 0.273

Gnomad OTH exome AF: 0.314

GnomAD4 exome AF: 0.274 AC: 399709 AN: 1459940 Hom.: 60750 Cov.: 37 AF XY: 0.269 AC XY: 195553 AN XY: 726250

African (AFR) AF: 0.718 AC: 24036 AN: 33468

American (AMR) AF: 0.414 AC: 18477 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 11467 AN: 26134

East Asian (EAS) AF: 0.0854 AC: 3391 AN: 39698

South Asian (SAS) AF: 0.180 AC: 15512 AN: 86210

European-Finnish (FIN) AF: 0.267 AC: 13966 AN: 52264

Middle Eastern (MID) AF: 0.364 AC: 1972 AN: 5418

European-Non Finnish (NFE) AF: 0.263 AC: 292372 AN: 1111792

Other (OTH) AF: 0.307 AC: 18516 AN: 60320

GnomAD4 genome AF: 0.395 AC: 60049 AN: 152124 Hom.: 14902 Cov.: 33 AF XY: 0.389 AC XY: 28942 AN XY: 74354

African (AFR) AF: 0.700 AC: 29033 AN: 41490

American (AMR) AF: 0.406 AC: 6206 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1485 AN: 3468

East Asian (EAS) AF: 0.104 AC: 536 AN: 5178

South Asian (SAS) AF: 0.180 AC: 869 AN: 4830

European-Finnish (FIN) AF: 0.256 AC: 2707 AN: 10584

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17845 AN: 67966

Other (OTH) AF: 0.396 AC: 836 AN: 2112

Alfa AF: 0.313 Hom.: 2793

Bravo AF: 0.424

TwinsUK AF: 0.246 AC: 911

ALSPAC AF: 0.263 AC: 1013

ESP6500AA AF: 0.680 AC: 2995

ESP6500EA AF: 0.274 AC: 2359

ExAC AF: 0.303 AC: 36666

Asia WGS AF: 0.225 AC: 785 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.53
DANN	Benign	0.65
DEOGEN2	Benign	0.055	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.077	N
LIST_S2	Benign	0.019	T
MetaRNN	Benign	0.0000033	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.045	N
PhyloP100		-0.11
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.011
Sift	Benign	0.67	T
Sift4G	Benign	0.57	T
Polyphen		0.0	B
Vest4		0.033
MPC		0.18
ClinPred		0.0054	T
GERP RS		-6.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.050
gMVP		0.14
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs9913430; hg19: chr17-48628470; COSMIC: COSV50065954; COSMIC: COSV50065954;