Variant 10-27743300-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_173576.3(MKX):c.116C>A(p.Ala39Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000569 in 1,405,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000057 ( 0 hom. )

Consequence

MKX
NM_173576.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.476

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.059399664).

BS2

High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MKX	NM_173576.3 linkuse as main transcript	c.116C>A	p.Ala39Asp	missense_variant	2/7	ENST00000419761.6	NP_775847.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MKX	ENST00000419761.6 linkuse as main transcript	c.116C>A	p.Ala39Asp	missense_variant	2/7	2	NM_173576.3	ENSP00000400896	P1
MKX	ENST00000375790.9 linkuse as main transcript	c.116C>A	p.Ala39Asp	missense_variant	2/7	1		ENSP00000364946	P1
MKX	ENST00000460919.2 linkuse as main transcript	c.116C>A	p.Ala39Asp	missense_variant	1/5	3		ENSP00000452751
MKX	ENST00000561227.1 linkuse as main transcript	c.116C>A	p.Ala39Asp	missense_variant	2/2	5		ENSP00000453746

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000259

AC:

AN:

193096

Hom.:

AF XY:

0.0000281

AC XY:

AN XY:

106818

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000217

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000569

AC:

AN:

1405652

Hom.:

Cov.:

AF XY:

0.00000717

AC XY:

AN XY:

697674

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000207

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:

0.00

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

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

Oct 31, 2022

The c.116C>A (p.A39D) alteration is located in exon 2 (coding exon 1) of the MKX gene. This alteration results from a C to A substitution at nucleotide position 116, causing the alanine (A) at amino acid position 39 to be replaced by an aspartic acid (D). 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

0.11

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.048

T;T;.;.

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.53

T;.;T;T

M_CAP

Benign

0.057

MetaRNN

Benign

0.059

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;N;.;.

MutationTaster

Benign

0.98

N;N

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.63

N;N;N;D

REVEL

Benign

0.14

Sift

Benign

0.12

T;T;T;T

Sift4G

Benign

0.31

T;T;.;T

Polyphen

0.0

B;B;.;.

Vest4

0.20

MutPred

0.21

Gain of catalytic residue at A39 (P = 0.0607);Gain of catalytic residue at A39 (P = 0.0607);Gain of catalytic residue at A39 (P = 0.0607);Gain of catalytic residue at A39 (P = 0.0607);

MVP

0.42

MPC

0.20

ClinPred

0.057

GERP RS

-1.2

Varity_R

0.10

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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