Variant rs121908134 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP5

The NM_031475.3(ESPN):c.2155A>C(p.Ser719Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,458,666 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

ESPN
NM_031475.3 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 2.11

Variant links:

Genes affected

ESPN (HGNC:13281): (espin) This gene encodes a multifunctional actin-bundling protein. It plays a major role in regulating the organization, dimensions, dynamics, and signaling capacities of the actin filament-rich, microvillus-type specializations that mediate sensory transduction in various mechanosensory and chemosensory cells. Mutations in this gene are associated with autosomal recessive neurosensory deafness, and autosomal dominant sensorineural deafness without vestibular involvement. [provided by RefSeq, Nov 2009]

ESPN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PP5

Variant 1-6451926-A-C is Pathogenic according to our data. Variant chr1-6451926-A-C is described in ClinVar as [Pathogenic]. Clinvar id is 4420.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-6451926-A-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESPN	NM_031475.3 linkuse as main transcript	c.2155A>C	p.Ser719Arg	missense_variant	10/13	ENST00000645284.1	NP_113663.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESPN	ENST00000645284.1 linkuse as main transcript	c.2155A>C	p.Ser719Arg	missense_variant	10/13		NM_031475.3	ENSP00000496593	P1	B1AK53-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000410

AC:

AN:

243942

Hom.:

AF XY:

0.00000755

AC XY:

AN XY:

132474

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000910

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1458666

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

725382

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:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000575

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000825

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Deafness, without vestibular involvement, autosomal dominant

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 01, 2006

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.50

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

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

Eigen

Benign

0.018

Eigen_PC

Benign

0.020

FATHMM_MKL

Benign

0.73

LIST_S2

Uncertain

0.86

.;D;D;D;D;D;D;T;D

M_CAP

Pathogenic

0.86

MetaRNN

Uncertain

0.71

D;D;D;D;D;D;D;D;D

MetaSVM

Uncertain

0.12

MutationAssessor

Benign

1.8

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

MutationTaster

Benign

0.081

A;A;A

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-2.6

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

REVEL

Uncertain

0.55

Sift

Uncertain

0.0010

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

Sift4G

Benign

0.17

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

Polyphen

0.76

P;.;P;.;P;.;.;.;.

Vest4

0.33, 0.71, 0.60

MutPred

0.47

Loss of glycosylation at S719 (P = 0.0017);Loss of glycosylation at S719 (P = 0.0017);Loss of glycosylation at S719 (P = 0.0017);.;.;.;.;.;.;

MVP

0.75

MPC

0.50

ClinPred

0.95

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.41

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

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