Variant 10-27741475-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4BS2

The NM_173576.3(MKX):c.218A>G(p.His73Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000345 in 1,448,572 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

MKX
NM_173576.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.15

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 Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.41243547).

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MKX	NM_173576.3 linkuse as main transcript	c.218A>G	p.His73Arg	missense_variant	3/7	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.218A>G	p.His73Arg	missense_variant	3/7	2	NM_173576.3	ENSP00000400896	P1
MKX	ENST00000375790.9 linkuse as main transcript	c.218A>G	p.His73Arg	missense_variant	3/7	1		ENSP00000364946	P1
MKX	ENST00000460919.2 linkuse as main transcript	c.218A>G	p.His73Arg	missense_variant	2/5	3		ENSP00000452751

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000345

AC:

AN:

1448572

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

720474

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000452

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Apr 06, 2024

The c.218A>G (p.H73R) alteration is located in exon 3 (coding exon 2) of the MKX gene. This alteration results from a A to G substitution at nucleotide position 218, causing the histidine (H) at amino acid position 73 to be replaced by an arginine (R). 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

Pathogenic

0.91

BayesDel_addAF

Uncertain

0.097

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

T;T;.

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.80

T;.;T

M_CAP

Benign

0.071

MetaRNN

Benign

0.41

T;T;T

MetaSVM

Benign

-0.80

MutationAssessor

Benign

0.97

L;L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-2.5

N;N;D

REVEL

Uncertain

0.31

Sift

Benign

0.12

T;T;T

Sift4G

Benign

0.27

T;T;.

Polyphen

0.99

D;D;.

Vest4

0.62

MutPred

0.28

Gain of methylation at K74 (P = 0.0744);Gain of methylation at K74 (P = 0.0744);Gain of methylation at K74 (P = 0.0744);

MVP

0.60

MPC

1.7

ClinPred

0.95

GERP RS

5.5

Varity_R

0.40

gMVP

0.49

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