9-137253150-G-C

Variant names:

• chr9-137253150-G-C
• NM_001004353.4:c.832G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001004353.4(STPG3):​c.832G>C​(p.Asp278His) 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. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: STPG3 NM_001004353.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.69

Genes affected

STPG3 (HGNC:37285): (sperm-tail PG-rich repeat containing 3) Predicted to be active in cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

CIMIP2A (HGNC:33818): (ciliary microtubule inner protein 2A) Located in ciliary basal body. [provided by Alliance of Genome Resources, Apr 2022]

STPG3-AS1 (HGNC:51176): (STPG3 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2691497).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STPG3	NM_001004353.4	c.832G>C	p.Asp278His	missense_variant	Exon 6 of 6	ENST00000412566.6	NP_001004353.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STPG3	ENST00000412566.6	c.832G>C	p.Asp278His	missense_variant	Exon 6 of 6	1	NM_001004353.4	ENSP00000391218.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 01, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.832G>C (p.D278H) alteration is located in exon 6 (coding exon 6) of the STPG3 gene. This alteration results from a G to C substitution at nucleotide position 832, causing the aspartic acid (D) at amino acid position 278 to be replaced by a histidine (H). 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	-0.036	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.044	T;.
Eigen	Benign	0.088
Eigen_PC	Benign	0.094
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.29	T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.27	T;T
MetaSVM	Benign	-0.94	T
PROVEAN	Uncertain	-4.0	.;D
REVEL	Benign	0.14
Sift	Uncertain	0.014	.;D
Sift4G	Uncertain	0.045	D;D
Polyphen		1.0	D;D
Vest4		0.48
MutPred		0.18		.;Loss of loop (P = 0.0804);
MVP		0.60
ClinPred		0.30	T
GERP RS		3.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: chr9-140147602;