Variant chr8-94646229-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_017697.4(ESRP1):c.437G>A(p.Cys146Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,612,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ESRP1
NM_017697.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.55

Variant links:

Genes affected

ESRP1 (HGNC:25966): (epithelial splicing regulatory protein 1) ESPR1 is an epithelial cell-type-specific splicing regulator (Warzecha et al., 2009 [PubMed 19285943]).[supplied by OMIM, Aug 2009]

ESRP1 links:

ESRP1 (HGNC:):

ESRP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.26583254).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESRP1	NM_017697.4 linkuse as main transcript	c.437G>A	p.Cys146Tyr	missense_variant	4/16	ENST00000433389.8	NP_060167.2	Q6NXG1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESRP1	ENST00000433389.8 linkuse as main transcript	c.437G>A	p.Cys146Tyr	missense_variant	4/16	1	NM_017697.4	ENSP00000405738.2		Q6NXG1-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248524

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134868

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000996

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460590

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726606

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 03, 2022

The c.437G>A (p.C146Y) alteration is located in exon 4 (coding exon 4) of the ESRP1 gene. This alteration results from a G to A substitution at nucleotide position 437, causing the cysteine (C) at amino acid position 146 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

0.31

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.0

CADD

Uncertain

DANN

Benign

0.45

DEOGEN2

Benign

0.038

.;T;T;.;.;.;T

Eigen

Benign

0.085

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.93

D;.;D;D;D;D;D

M_CAP

Benign

0.0069

MetaRNN

Benign

0.27

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;L;L;L;L;.;.

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-1.9

N;N;.;N;.;N;N

REVEL

Benign

0.19

Sift

Benign

1.0

T;T;.;T;.;T;T

Sift4G

Benign

1.0

T;T;.;T;.;T;T

Polyphen

0.37, 0.13, 0.018

.;B;B;B;B;.;.

Vest4

0.79

MutPred

0.41

Loss of methylation at K145 (P = 0.014);Loss of methylation at K145 (P = 0.014);Loss of methylation at K145 (P = 0.014);Loss of methylation at K145 (P = 0.014);Loss of methylation at K145 (P = 0.014);Loss of methylation at K145 (P = 0.014);.;

MVP

0.81

MPC

1.1

ClinPred

0.29

GERP RS

3.6

Varity_R

0.12

gMVP

0.64

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over