Variant X-139602462-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_001171876.2(MCF2):c.2008A>G(p.Asn670Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 1,200,241 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 426 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00087 ( 0 hom., 20 hem., cov: 23)

Exomes 𝑓: 0.0012 ( 0 hom. 406 hem. )

Consequence

MCF2
NM_001171876.2 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.91

Variant links:

Genes affected

MCF2 (HGNC:6940): (MCF.2 cell line derived transforming sequence) The oncogenic protein encoded by this gene is a guanine nucleotide exchange factor (GEF) that exerts control over some members of the Rho family of small GTPases. Several transcript variants encoding different isoforms have been found for this gene. These isoforms exhibit different expression patterns and varying levels of GEF activity.[provided by RefSeq, Jan 2010]

MCF2 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=0.0896844).

BP6

Variant X-139602462-T-C is Benign according to our data. Variant chrX-139602462-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 378121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd4 at 20 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCF2	NM_001171876.2 linkuse as main transcript	c.2008A>G	p.Asn670Asp	missense_variant	20/29	ENST00000519895.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCF2	ENST00000519895.6 linkuse as main transcript	c.2008A>G	p.Asn670Asp	missense_variant	20/29	2	NM_001171876.2	P4	P10911-5

Frequencies

GnomAD3 genomes

AF:

0.000873

AC:

AN:

112249

Hom.:

Cov.:

AF XY:

0.000582

AC XY:

AN XY:

34393

show subpopulations

Gnomad AFR

AF:

0.000323

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00165

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000826

AC:

145

AN:

175452

Hom.:

AF XY:

0.000793

AC XY:

AN XY:

60562

show subpopulations

Gnomad AFR exome

AF:

0.000235

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:

0.00171

Gnomad OTH exome

AF:

0.00140

GnomAD4 exome

AF:

0.00115

AC:

1255

AN:

1087937

Hom.:

Cov.:

AF XY:

0.00115

AC XY:

406

AN XY:

353923

show subpopulations

Gnomad4 AFR exome

AF:

0.0000766

Gnomad4 AMR exome

AF:

0.0000290

Gnomad4 ASJ exome

AF:

0.000104

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000954

Gnomad4 FIN exome

AF:

0.0000741

Gnomad4 NFE exome

AF:

0.00145

Gnomad4 OTH exome

AF:

0.000700

GnomAD4 genome

AF:

0.000873

AC:

AN:

112304

Hom.:

Cov.:

AF XY:

0.000580

AC XY:

AN XY:

34458

show subpopulations

Gnomad4 AFR

AF:

0.000323

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00165

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00158

Hom.:

Bravo

AF:

0.000786

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00163

AC:

ExAC

AF:

0.000947

AC:

115

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 15, 2015

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.88

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.46

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

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

1.0

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

M_CAP

Pathogenic

0.33

MetaRNN

Benign

0.090

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

MetaSVM

Uncertain

-0.16

MutationAssessor

Pathogenic

3.0

.;M;.;.;.;.;M;.

MutationTaster

Benign

1.0

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

PrimateAI

Uncertain

0.65

PROVEAN

Pathogenic

-4.6

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

REVEL

Uncertain

0.53

Sift

Pathogenic

0.0

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

Sift4G

Pathogenic

0.0

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

Polyphen

0.53, 0.92, 0.18

.;P;.;.;.;.;P;B

Vest4

0.85, 0.83, 0.83, 0.83, 0.85

MVP

0.92

MPC

0.50

ClinPred

0.15

GERP RS

5.6

Varity_R

0.94

gMVP

0.73

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