chr17-50549049-A-G

Position:

• chr17-50549049-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_022827.4(SPATA20):​c.523A>G​(p.Ser175Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SPATA20 NM_022827.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.74

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATA20	NM_022827.4	c.523A>G	p.Ser175Gly	missense_variant	6/17	ENST00000006658.11	NP_073738.2
SPATA20	NM_001258372.2	c.475A>G	p.Ser159Gly	missense_variant	5/16		NP_001245301.1
SPATA20	NM_001258373.2	c.343A>G	p.Ser115Gly	missense_variant	6/17		NP_001245302.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPATA20	ENST00000006658.11	c.523A>G	p.Ser175Gly	missense_variant	6/17	1	NM_022827.4	ENSP00000006658

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 03, 2024

The c.523A>G (p.S175G) alteration is located in exon 6 (coding exon 6) of the SPATA20 gene. This alteration results from a A to G substitution at nucleotide position 523, causing the serine (S) at amino acid position 175 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	.;.;T;T
Eigen	Benign	0.082
Eigen_PC	Benign	0.20
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.89	D;D;D;D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.59	D;D;D;D
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.0	.;.;L;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-2.5	.;D;D;.
REVEL	Benign	0.14
Sift	Benign	0.040	.;D;D;.
Sift4G	Benign	0.083	T;T;T;T
Polyphen		0.034, 0.20	.;B;B;.
Vest4		0.64
MutPred		0.43		.;.;Loss of loop (P = 0.1242);Loss of loop (P = 0.1242);
MVP		0.51
MPC		0.39
ClinPred		0.93	D
GERP RS		4.9
Varity_R		0.32
gMVP		0.67

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-48626410;