Variant 3-39184276-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_194293.4(XIRP1):c.5170A>G(p.Ile1724Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0024 in 1,614,180 control chromosomes in the GnomAD database, including 81 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.013 ( 36 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 45 hom. )

Consequence

XIRP1
NM_194293.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.25

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017963946).

BP6

Variant 3-39184276-T-C is Benign according to our data. Variant chr3-39184276-T-C is described in ClinVar as [Benign]. Clinvar id is 767894.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0131 (1989/152316) while in subpopulation AFR AF= 0.0447 (1856/41556). AF 95% confidence interval is 0.043. There are 36 homozygotes in gnomad4. There are 942 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 36 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XIRP1	NM_194293.4 linkuse as main transcript	c.5170A>G	p.Ile1724Val	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.5170A>G	p.Ile1724Val	missense_variant	2/2	1	NM_194293.4	A2	Q702N8-1
XIRP1	ENST00000421646.1 linkuse as main transcript	c.1219A>G	p.Ile407Val	missense_variant	2/2	1			Q702N8-3
XIRP1	ENST00000396251.1 linkuse as main transcript	c.*1377A>G		3_prime_UTR_variant	3/3	1		P2	Q702N8-2

Frequencies

GnomAD3 genomes

AF:

0.0130

AC:

1985

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0448

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00569

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.0143

GnomAD3 exomes

AF:

0.00336

AC:

844

AN:

251408

Hom.:

AF XY:

0.00244

AC XY:

332

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.0432

Gnomad AMR exome

AF:

0.00315

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000149

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00129

AC:

1883

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

802

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.0429

Gnomad4 AMR exome

AF:

0.00344

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000674

Gnomad4 OTH exome

AF:

0.00306

GnomAD4 genome

AF:

0.0131

AC:

1989

AN:

152316

Hom.:

Cov.:

AF XY:

0.0126

AC XY:

942

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0447

Gnomad4 AMR

AF:

0.00568

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.0156

Alfa

AF:

0.00275

Hom.:

Bravo

AF:

0.0147

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0409

AC:

180

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00419

AC:

509

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

XIRP1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 19, 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). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.077

DANN

Benign

0.23

DEOGEN2

Benign

0.041

T;.

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0022

LIST_S2

Benign

0.26

T;T

MetaRNN

Benign

0.0018

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.6

N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

0.36

N;N

REVEL

Benign

0.11

Sift

Benign

1.0

T;T

Sift4G

Benign

0.69

T;T

Polyphen

0.0

B;.

Vest4

0.025

MVP

0.040

MPC

0.059

ClinPred

0.0015

GERP RS

1.7

Varity_R

0.019

gMVP

0.040

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