Variant 3-39184261-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_194293.4(XIRP1):c.5185G>C(p.Val1729Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0209 in 1,614,032 control chromosomes in the GnomAD database, including 3,356 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 (no stars).

Frequency

Genomes: 𝑓 0.085 ( 1517 hom., cov: 32)

Exomes 𝑓: 0.014 ( 1839 hom. )

Consequence

XIRP1
NM_194293.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0510

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004863888).

BP6

Variant 3-39184261-C-G is Benign according to our data. Variant chr3-39184261-C-G is described in ClinVar as [Benign]. Clinvar id is 3059743.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XIRP1	NM_194293.4 linkuse as main transcript	c.5185G>C	p.Val1729Leu	missense_variant	2/2	ENST00000340369.4	NP_919269.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XIRP1	ENST00000340369.4 linkuse as main transcript	c.5185G>C	p.Val1729Leu	missense_variant	2/2	1	NM_194293.4	ENSP00000343140	A2	Q702N8-1
XIRP1	ENST00000421646.1 linkuse as main transcript	c.1234G>C	p.Val412Leu	missense_variant	2/2	1		ENSP00000391645		Q702N8-3
XIRP1	ENST00000396251.1 linkuse as main transcript	c.*1392G>C		3_prime_UTR_variant	3/3	1		ENSP00000379550	P2	Q702N8-2

Frequencies

GnomAD3 genomes

AF:

0.0849

AC:

12907

AN:

152108

Hom.:

1515

Cov.:

show subpopulations

Gnomad AFR

AF:

0.260

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.105

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.0459

Gnomad SAS

AF:

0.0108

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.00170

Gnomad OTH

AF:

0.0675

GnomAD3 exomes

AF:

0.0429

AC:

10787

AN:

251356

Hom.:

1015

AF XY:

0.0329

AC XY:

4470

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.272

Gnomad AMR exome

AF:

0.140

Gnomad ASJ exome

AF:

0.00258

Gnomad EAS exome

AF:

0.0469

Gnomad SAS exome

AF:

0.00983

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00147

Gnomad OTH exome

AF:

0.0282

GnomAD4 exome

AF:

0.0142

AC:

20724

AN:

1461806

Hom.:

1839

Cov.:

AF XY:

0.0125

AC XY:

9090

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.273

Gnomad4 AMR exome

AF:

0.134

Gnomad4 ASJ exome

AF:

0.00260

Gnomad4 EAS exome

AF:

0.0408

Gnomad4 SAS exome

AF:

0.00814

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00132

Gnomad4 OTH exome

AF:

0.0269

GnomAD4 genome

AF:

0.0850

AC:

12935

AN:

152226

Hom.:

1517

Cov.:

AF XY:

0.0840

AC XY:

6254

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.260

Gnomad4 AMR

AF:

0.105

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.0459

Gnomad4 SAS

AF:

0.0108

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00171

Gnomad4 OTH

AF:

0.0668

Alfa

AF:

0.0151

Hom.:

185

Bravo

AF:

0.104

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.253

AC:

1115

ESP6500EA

AF:

0.00244

AC:

ExAC

AF:

0.0414

AC:

5022

Asia WGS

AF:

0.0530

AC:

185

AN:

3478

EpiCase

AF:

0.00136

EpiControl

AF:

0.00172

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

Nov 06, 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

0.092

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.56

DANN

Benign

0.85

DEOGEN2

Benign

0.049

T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.48

T;T

MetaRNN

Benign

0.0049

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

N;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.10

N;N

REVEL

Benign

0.065

Sift

Benign

0.27

T;T

Sift4G

Benign

0.73

T;T

Polyphen

0.0050

B;.

Vest4

0.049

MutPred

0.13

Loss of sheet (P = 0.0054);.;

MPC

0.067

ClinPred

0.00012

GERP RS

1.4

Varity_R

0.051

gMVP

0.064

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