Variant 3-39184144-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_194293.4(XIRP1):c.5302G>A(p.Val1768Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000664 in 1,612,432 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0029 ( 6 hom., cov: 32)

Exomes 𝑓: 0.00043 ( 4 hom. )

Consequence

XIRP1
NM_194293.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.48

Variant links:

Genes affected

XIRP1 (HGNC:14301): (xin actin binding repeat containing 1) The protein encoded by this gene is a striated muscle protein and belongs to the Xin actin-binding repeat-containing protein (XIRP) family. The protein functions to protect actin filaments during depolymerization. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2017]

XIRP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0043652654).

BP6

Variant 3-39184144-C-T is Benign according to our data. Variant chr3-39184144-C-T is described in ClinVar as [Benign]. Clinvar id is 3038432.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XIRP1	NM_194293.4 linkuse as main transcript	c.5302G>A	p.Val1768Met	missense_variant	2/2	ENST00000340369.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XIRP1	ENST00000340369.4 linkuse as main transcript	c.5302G>A	p.Val1768Met	missense_variant	2/2	1	NM_194293.4	A2	Q702N8-1
XIRP1	ENST00000421646.1 linkuse as main transcript	c.1351G>A	p.Val451Met	missense_variant	2/2	1			Q702N8-3
XIRP1	ENST00000396251.1 linkuse as main transcript	c.*1509G>A		3_prime_UTR_variant	3/3	1		P2	Q702N8-2

Frequencies

GnomAD3 genomes

AF:

0.00281

AC:

428

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00926

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000891

AC:

223

AN:

250260

Hom.:

AF XY:

0.000777

AC XY:

105

AN XY:

135184

show subpopulations

Gnomad AFR exome

AF:

0.0106

Gnomad AMR exome

AF:

0.000667

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000330

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000212

Gnomad OTH exome

AF:

0.000493

GnomAD4 exome

AF:

0.000434

AC:

634

AN:

1460098

Hom.:

Cov.:

AF XY:

0.000401

AC XY:

291

AN XY:

726080

show subpopulations

Gnomad4 AFR exome

AF:

0.0114

Gnomad4 AMR exome

AF:

0.000807

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000698

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000129

Gnomad4 OTH exome

AF:

0.00109

GnomAD4 genome

AF:

0.00287

AC:

437

AN:

152334

Hom.:

Cov.:

AF XY:

0.00274

AC XY:

204

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00945

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000220

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000574

Hom.:

Bravo

AF:

0.00351

ESP6500AA

AF:

0.00931

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00105

AC:

127

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000297

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

XIRP1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 27, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

T;.

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.73

T;T

MetaRNN

Benign

0.0044

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

L;.

MutationTaster

Benign

0.86

D;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.1

N;D

REVEL

Benign

0.060

Sift

Benign

0.042

D;D

Sift4G

Uncertain

0.0080

D;T

Polyphen

0.49

P;.

Vest4

0.12

MVP

0.092

MPC

0.073

ClinPred

0.018

GERP RS

0.098

Varity_R

0.053

gMVP

0.18

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