chr4-97712802-T-C

Position:

• chr4-97712802-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_174952.3(STPG2):​c.1217A>G​(p.Tyr406Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: STPG2 NM_174952.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.17

Genes affected

STPG2 (HGNC:28712): (sperm tail PG-rich repeat containing 2)

STPG2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.768

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STPG2	NM_174952.3	c.1217A>G	p.Tyr406Cys	missense_variant	10/11	ENST00000295268.4	NP_777612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STPG2	ENST00000295268.4	c.1217A>G	p.Tyr406Cys	missense_variant	10/11	1	NM_174952.3	ENSP00000295268.3
STPG2	ENST00000522676.5	c.359A>G	p.Tyr120Cys	missense_variant	4/5	1		ENSP00000428346.1
STPG2	ENST00000506482.1	n.165A>G		non_coding_transcript_exon_variant	2/5	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Sep 27, 2024

The c.1217A>G (p.Y406C) alteration is located in exon 10 (coding exon 10) of the STPG2 gene. This alteration results from a A to G substitution at nucleotide position 1217, causing the tyrosine (Y) at amino acid position 406 to be replaced by a cysteine (C). 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	0.31
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	.;T
Eigen	Uncertain	0.31
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.64	T;T
M_CAP	Benign	0.050	D
MetaRNN	Pathogenic	0.77	D;D
MetaSVM	Uncertain	0.060	D
MutationAssessor	Uncertain	2.5	.;M
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-7.9	D;D
REVEL	Uncertain	0.47
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.0080	D;D
Polyphen		1.0	.;D
Vest4		0.60
MutPred		0.63		.;Loss of phosphorylation at Y406 (P = 0.0134);
MVP		0.33
MPC		0.11
ClinPred		1.0	D
GERP RS		3.6
Varity_R		0.53
gMVP		0.77

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: rs1158533312; hg19: chr4-98633953;