Variant X-139589842-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001171876.2(MCF2):c.2591T>C(p.Ile864Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00192 in 1,188,806 control chromosomes in the GnomAD database, including 36 homozygotes. There are 611 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 18 hom., 328 hem., cov: 23)

Exomes 𝑓: 0.0011 ( 18 hom. 283 hem. )

Consequence

MCF2
NM_001171876.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.39

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007697314).

BP6

Variant X-139589842-A-G is Benign according to our data. Variant chrX-139589842-A-G is described in ClinVar as [Benign]. Clinvar id is 777845.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0103 (1149/111785) while in subpopulation AFR AF= 0.0345 (1063/30820). AF 95% confidence interval is 0.0328. There are 18 homozygotes in gnomad4. There are 328 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 18 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCF2	NM_001171876.2 linkuse as main transcript	c.2591T>C	p.Ile864Thr	missense_variant	24/29	ENST00000519895.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCF2	ENST00000519895.6 linkuse as main transcript	c.2591T>C	p.Ile864Thr	missense_variant	24/29	2	NM_001171876.2	P4	P10911-5

Frequencies

GnomAD3 genomes

AF:

0.0103

AC:

1148

AN:

111733

Hom.:

Cov.:

AF XY:

0.00967

AC XY:

328

AN XY:

33911

show subpopulations

Gnomad AFR

AF:

0.0345

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00622

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:

0.000169

Gnomad OTH

AF:

0.00797

GnomAD3 exomes

AF:

0.00316

AC:

529

AN:

167259

Hom.:

AF XY:

0.00187

AC XY:

103

AN XY:

55151

show subpopulations

Gnomad AFR exome

AF:

0.0349

Gnomad AMR exome

AF:

0.00352

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:

0.0000516

Gnomad OTH exome

AF:

0.00246

GnomAD4 exome

AF:

0.00105

AC:

1132

AN:

1077021

Hom.:

Cov.:

AF XY:

0.000816

AC XY:

283

AN XY:

346923

show subpopulations

Gnomad4 AFR exome

AF:

0.0342

Gnomad4 AMR exome

AF:

0.00351

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:

0.0000446

Gnomad4 OTH exome

AF:

0.00238

GnomAD4 genome

AF:

0.0103

AC:

1149

AN:

111785

Hom.:

Cov.:

AF XY:

0.00965

AC XY:

328

AN XY:

33973

show subpopulations

Gnomad4 AFR

AF:

0.0345

Gnomad4 AMR

AF:

0.00621

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000169

Gnomad4 OTH

AF:

0.00787

Alfa

AF:

0.00116

Hom.:

Bravo

AF:

0.0116

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0305

AC:

117

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.00333

AC:

404

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

0.18

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

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

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.96

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

MetaRNN

Benign

0.0077

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

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

MutationTaster

Benign

0.68

N;N;N;N;N;N;N;N

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-4.4

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

REVEL

Benign

0.13

Sift

Uncertain

0.026

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

Sift4G

Benign

0.087

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

Polyphen

0.84, 0.76, 0.99

.;P;.;.;.;.;P;D

Vest4

0.24, 0.25, 0.22, 0.23, 0.21, 0.24

MVP

0.37

MPC

0.40

ClinPred

0.052

GERP RS

4.8

Varity_R

0.58

gMVP

0.48

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