dbSNP rs752500845: MKX:p.Gly44Cys (chr10-27743286-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_173576.3(MKX):c.130G>T(p.Gly44Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,399,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G44R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MKX
NM_173576.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.03

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27346006).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MKX	NM_173576.3 link	c.130G>T	p.Gly44Cys	missense_variant	Exon 2 of 7	ENST00000419761.6	NP_775847.2	Q8IYA7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MKX	ENST00000419761.6 link	c.130G>T	p.Gly44Cys	missense_variant	Exon 2 of 7	2	NM_173576.3	ENSP00000400896.1	Q8IYA7
MKX	ENST00000375790.9 link	c.130G>T	p.Gly44Cys	missense_variant	Exon 2 of 7	1		ENSP00000364946.4	Q8IYA7
MKX	ENST00000460919.2 link	c.130G>T	p.Gly44Cys	missense_variant	Exon 1 of 5	3		ENSP00000452751.1	H0YKC7
MKX	ENST00000561227.1 link	c.130G>T	p.Gly44Cys	missense_variant	Exon 2 of 2	5		ENSP00000453746.1	H0YMU2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000529

AC:

AN:

189054

AF XY:

0.00000955

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000143

AC:

AN:

1399688

Hom.:

Cov.:

AF XY:

0.00000288

AC XY:

AN XY:

694284

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

28780

American (AMR)

AF:

0.00

AC:

AN:

32724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24038

East Asian (EAS)

AF:

0.00

AC:

AN:

34406

South Asian (SAS)

AF:

0.0000130

AC:

AN:

76698

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52334

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5582

European-Non Finnish (NFE)

AF:

9.20e-7

AC:

AN:

1087332

Other (OTH)

AF:

0.00

AC:

AN:

57794

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00666416), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000826

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

T;T;.;.

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.72

T;.;T;T

M_CAP

Pathogenic

0.30

MetaRNN

Benign

0.27

T;T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

0.69

N;N;.;.

PhyloP100

2.0

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.7

N;N;N;D

REVEL

Benign

0.058

Sift

Uncertain

0.014

D;D;D;D

Sift4G

Benign

0.079

T;T;.;T

Polyphen

0.70

P;P;.;.

Vest4

0.40

MutPred

0.23

Gain of catalytic residue at A39 (P = 0.1657);Gain of catalytic residue at A39 (P = 0.1657);Gain of catalytic residue at A39 (P = 0.1657);Gain of catalytic residue at A39 (P = 0.1657);

MVP

0.38

MPC

0.34

ClinPred

0.77

GERP RS

4.4

PromoterAI

-0.11

Neutral

(source)

Varity_R

0.26

gMVP

0.42

Mutation Taster

=81/19

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over