Variant chrX-139589884-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001171876.2(MCF2):c.2549G>A(p.Arg850His) variant causes a missense change. The variant allele was found at a frequency of 0.00001 in 1,194,189 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000092 ( 0 hom. 3 hem. )

Consequence

MCF2
NM_001171876.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.80

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCF2	NM_001171876.2 linkuse as main transcript	c.2549G>A	p.Arg850His	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.2549G>A	p.Arg850His	missense_variant	24/29	2	NM_001171876.2	P4	P10911-5

Frequencies

GnomAD3 genomes

AF:

0.0000180

AC:

AN:

111411

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33615

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000168

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000924

AC:

AN:

1082778

Hom.:

Cov.:

AF XY:

0.00000855

AC XY:

AN XY:

350832

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000337

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000248

Gnomad4 NFE exome

AF:

0.00000840

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000180

AC:

AN:

111411

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33615

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000168

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 13, 2023

The c.2549G>A (p.R850H) alteration is located in exon 24 (coding exon 23) of the MCF2 gene. This alteration results from a G to A substitution at nucleotide position 2549, causing the arginine (R) at amino acid position 850 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.054

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.43

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

FATHMM_MKL

Uncertain

0.89

LIST_S2

Pathogenic

0.99

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

M_CAP

Benign

0.081

MetaRNN

Uncertain

0.52

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

MetaSVM

Benign

-0.76

MutationAssessor

Uncertain

2.5

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

MutationTaster

Benign

0.70

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

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.7

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

REVEL

Benign

0.28

Sift

Uncertain

0.0020

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

Sift4G

Uncertain

0.041

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

Polyphen

1.0

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

Vest4

0.39, 0.41, 0.35, 0.38, 0.36, 0.39

MVP

0.72

MPC

0.98

ClinPred

1.0

GERP RS

5.9

Varity_R

0.68

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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