Variant 10-27743297-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_173576.3(MKX):c.119G>A(p.Arg40His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00408 in 1,553,150 control chromosomes in the GnomAD database, including 240 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.022 ( 140 hom., cov: 33)

Exomes 𝑓: 0.0021 ( 100 hom. )

Consequence

MKX
NM_173576.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.96

Variant links:

Genes affected

MKX (HGNC:23729): (mohawk homeobox) The protein encoded by this gene is an IRX family-related homeobox protein that may play a role in cell adhesion. Studies in mice suggest that this protein may be a regulator of tendon development. Two transcript variants encoding the same protein have been found for this gene.[provided by RefSeq, Jun 2011]

MKX 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=0.0020515919).

BP6

Variant 10-27743297-C-T is Benign according to our data. Variant chr10-27743297-C-T is described in ClinVar as [Benign]. Clinvar id is 768355.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MKX	NM_173576.3 linkuse as main transcript	c.119G>A	p.Arg40His	missense_variant	2/7	ENST00000419761.6	NP_775847.2	Q8IYA7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MKX	ENST00000419761.6 linkuse as main transcript	c.119G>A	p.Arg40His	missense_variant	2/7	2	NM_173576.3	ENSP00000400896.1	Q8IYA7
MKX	ENST00000375790.9 linkuse as main transcript	c.119G>A	p.Arg40His	missense_variant	2/7	1		ENSP00000364946.4	Q8IYA7
MKX	ENST00000460919.2 linkuse as main transcript	c.119G>A	p.Arg40His	missense_variant	1/5	3		ENSP00000452751.1	H0YKC7
MKX	ENST00000561227.1 linkuse as main transcript	c.119G>A	p.Arg40His	missense_variant	2/2	5		ENSP00000453746.1	H0YMU2

Frequencies

GnomAD3 genomes

AF:

0.0221

AC:

3356

AN:

152170

Hom.:

132

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0760

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00916

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.0187

GnomAD3 exomes

AF:

0.00519

AC:

975

AN:

187894

Hom.:

AF XY:

0.00386

AC XY:

402

AN XY:

104198

show subpopulations

Gnomad AFR exome

AF:

0.0771

Gnomad AMR exome

AF:

0.00348

Gnomad ASJ exome

AF:

0.00118

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000401

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000289

Gnomad OTH exome

AF:

0.00332

GnomAD4 exome

AF:

0.00211

AC:

2954

AN:

1400862

Hom.:

100

Cov.:

AF XY:

0.00188

AC XY:

1310

AN XY:

695080

show subpopulations

Gnomad4 AFR exome

AF:

0.0751

Gnomad4 AMR exome

AF:

0.00406

Gnomad4 ASJ exome

AF:

0.00121

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000274

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000190

Gnomad4 OTH exome

AF:

0.00612

GnomAD4 genome

AF:

0.0222

AC:

3387

AN:

152288

Hom.:

140

Cov.:

AF XY:

0.0222

AC XY:

1653

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0766

Gnomad4 AMR

AF:

0.00908

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.0185

Alfa

AF:

0.0103

Hom.:

Bravo

AF:

0.0262

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0753

AC:

331

ESP6500EA

AF:

0.000466

AC:

ExAC

AF:

0.00697

AC:

843

Asia WGS

AF:

0.00982

AC:

AN:

3478

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.029

T;T;.;.

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.73

T;.;T;T

MetaRNN

Benign

0.0021

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N;.;.

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.13

N;N;N;N

REVEL

Benign

0.059

Sift

Benign

0.21

T;T;T;T

Sift4G

Benign

0.64

T;T;.;T

Polyphen

0.0

B;B;.;.

Vest4

0.15

MVP

0.41

MPC

0.16

ClinPred

0.018

GERP RS

2.1

Varity_R

0.050

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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