Variant 13-112979696-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001320816.2(MCF2L):c.29C>A(p.Thr10Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00142 in 1,612,932 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 1 hom., cov: 34)

Exomes 𝑓: 0.0014 ( 4 hom. )

Consequence

MCF2L
NM_001320816.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.499

Variant links:

Genes affected

MCF2L (HGNC:14576): (MCF.2 cell line derived transforming sequence like) This gene encodes a guanine nucleotide exchange factor that interacts specifically with the GTP-bound Rac1 and plays a role in the Rho/Rac signaling pathways. A variant in this gene was associated with osteoarthritis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

MCF2L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004922658).

BP6

Variant 13-112979696-C-A is Benign according to our data. Variant chr13-112979696-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2643971.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCF2L	NM_001112732.3 linkuse as main transcript	c.79+10238C>A		intron_variant		ENST00000535094.7	NP_001106203.2	O15068-9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCF2L	ENST00000535094.7 linkuse as main transcript	c.79+10238C>A		intron_variant		2	NM_001112732.3	ENSP00000440374.2		O15068-9

Frequencies

GnomAD3 genomes

AF:

0.00172

AC:

262

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00360

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00275

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00117

AC:

288

AN:

246394

Hom.:

AF XY:

0.00121

AC XY:

163

AN XY:

134542

show subpopulations

Gnomad AFR exome

AF:

0.000133

Gnomad AMR exome

AF:

0.000987

Gnomad ASJ exome

AF:

0.000101

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000794

Gnomad NFE exome

AF:

0.00202

Gnomad OTH exome

AF:

0.00167

GnomAD4 exome

AF:

0.00139

AC:

2031

AN:

1460618

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

993

AN XY:

726610

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.000962

Gnomad4 ASJ exome

AF:

0.000191

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00134

Gnomad4 NFE exome

AF:

0.00164

Gnomad4 OTH exome

AF:

0.00121

GnomAD4 genome

AF:

0.00172

AC:

262

AN:

152314

Hom.:

Cov.:

AF XY:

0.00171

AC XY:

127

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00359

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00275

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00271

Hom.:

Bravo

AF:

0.00156

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00154

AC:

ExAC

AF:

0.00112

AC:

135

EpiCase

AF:

0.00185

EpiControl

AF:

0.00166

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2022

MCF2L: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.69

CADD

Benign

7.5

DANN

Benign

0.91

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.36

M_CAP

Benign

0.011

MetaRNN

Benign

0.0049

MetaSVM

Benign

-1.0

PROVEAN

Benign

-0.090

REVEL

Benign

0.0090

Sift

Pathogenic

0.0

Vest4

0.10

MVP

0.28

ClinPred

0.063

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Splicing

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