4-97943964-G-C

Position:

• chr4-97943964-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_174952.3(STPG2):​c.977C>G​(p.Pro326Arg) 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 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: not found (cov: 32)
• Consequence: STPG2 NM_174952.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.331

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.073842466).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STPG2	NM_174952.3	c.977C>G	p.Pro326Arg	missense_variant	8/11	ENST00000295268.4	NP_777612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STPG2	ENST00000295268.4	c.977C>G	p.Pro326Arg	missense_variant	8/11	1	NM_174952.3	ENSP00000295268.3
STPG2	ENST00000522676.5	c.119C>G	p.Pro40Arg	missense_variant	2/5	1		ENSP00000428346.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Nov 10, 2024

The c.977C>G (p.P326R) alteration is located in exon 8 (coding exon 8) of the STPG2 gene. This alteration results from a C to G substitution at nucleotide position 977, causing the proline (P) at amino acid position 326 to be replaced by an arginine (R). 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	0.12
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	16
DANN	Benign	0.42
DEOGEN2	Benign	0.0018	.;T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.46	T;T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.074	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.11	.;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.050
Sift	Benign	0.21	T;T
Sift4G	Benign	0.28	T;T
Polyphen		0.0050	.;B
Vest4		0.43
MutPred		0.47		.;Gain of MoRF binding (P = 0.0087);
MVP		0.092
MPC		0.015
ClinPred		0.042	T
GERP RS		1.1
Varity_R		0.088
gMVP		0.23

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-98865115;