Variant 10-27734672-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173576.3(MKX):c.622G>A(p.Ala208Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MKX
NM_173576.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.70

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1661722).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MKX	NM_173576.3 linkuse as main transcript	c.622G>A	p.Ala208Thr	missense_variant	5/7	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.622G>A	p.Ala208Thr	missense_variant	5/7	2	NM_173576.3	ENSP00000400896.1	Q8IYA7
MKX	ENST00000375790.9 linkuse as main transcript	c.622G>A	p.Ala208Thr	missense_variant	5/7	1		ENSP00000364946.4	Q8IYA7
MKX	ENST00000460919.2 linkuse as main transcript	c.622G>A	p.Ala208Thr	missense_variant	4/5	3		ENSP00000452751.1	H0YKC7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727246

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Aug 02, 2021

The c.622G>A (p.A208T) alteration is located in exon 5 (coding exon 4) of the MKX gene. This alteration results from a G to A substitution at nucleotide position 622, causing the alanine (A) at amino acid position 208 to be replaced by a threonine (T). 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

0.067

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.058

T;T;.

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.076

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.77

T;.;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.17

T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.97

L;L;.

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.85

N;N;N

REVEL

Benign

0.056

Sift

Benign

0.14

T;T;T

Sift4G

Benign

0.33

T;T;.

Polyphen

0.0010

B;B;.

Vest4

0.17

MutPred

0.18

Gain of phosphorylation at A208 (P = 0.0286);Gain of phosphorylation at A208 (P = 0.0286);Gain of phosphorylation at A208 (P = 0.0286);

MVP

0.51

MPC

0.12

ClinPred

0.32

GERP RS

2.6

Varity_R

0.061

gMVP

0.18

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over