13-42953958-G-A

Position:

• chr13-42953958-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_033255.5(EPSTI1):​c.553C>T​(p.His185Tyr) 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. 14/21 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: 33)
• Consequence: EPSTI1 NM_033255.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.42

Genes affected

EPSTI1 (HGNC:16465): (epithelial stromal interaction 1) The protein encoded by this gene has been shown to promote tumor invasion and metastasis in some invasive cancer cells when overexpressed. Expression of this gene has been shown to be upregulated by direct binding of the Kruppel like factor 8 protein to promoter sequences. The translated protein interacts with the amino terminal region of the valosin containing protein gene product, resulting in the nuclear translocation of the nuclear factor kappa B subunit 1 gene product, and activation of target genes. Overexpression of this gene has been observed in some breast cancers and in some individuals with systemic lupus erythematosus (SLE). [provided by RefSeq, Sep 2016]

EPSTI1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.055705428).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPSTI1	NM_033255.5	c.553C>T	p.His185Tyr	missense_variant	6/11	ENST00000313624.12	NP_150280.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPSTI1	ENST00000313624.12	c.553C>T	p.His185Tyr	missense_variant	6/11	1	NM_033255.5	ENSP00000318643.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

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

Aug 20, 2024

The c.553C>T (p.H185Y) alteration is located in exon 6 (coding exon 6) of the EPSTI1 gene. This alteration results from a C to T substitution at nucleotide position 553, causing the histidine (H) at amino acid position 185 to be replaced by a tyrosine (Y). 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	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	20
DANN	Benign	0.93
DEOGEN2	Benign	0.081	.;.;T;T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.70	T;T;T;T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.056	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;L;L;.
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.2	D;D;D;D
REVEL	Benign	0.058
Sift	Benign	0.084	T;T;T;T
Sift4G	Benign	0.47	T;T;T;.
Polyphen		0.053	B;B;.;.
Vest4		0.43
MutPred		0.14		Gain of phosphorylation at H185 (P = 0.0709);Gain of phosphorylation at H185 (P = 0.0709);Gain of phosphorylation at H185 (P = 0.0709);.;
MVP		0.12
MPC		0.20
ClinPred		0.28	T
GERP RS		4.0
Varity_R		0.074
gMVP		0.063

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr13-43528094;