10-27743313-C-G

Position:

• chr10-27743313-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173576.3(MKX):​c.103G>C​(p.Asp35His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: MKX NM_173576.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.93

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]

ACMG classification

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=0.2591532).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MKX	NM_173576.3	c.103G>C	p.Asp35His	missense_variant	2/7	ENST00000419761.6	NP_775847.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MKX	ENST00000419761.6	c.103G>C	p.Asp35His	missense_variant	2/7	2	NM_173576.3	ENSP00000400896	P1
MKX	ENST00000375790.9	c.103G>C	p.Asp35His	missense_variant	2/7	1		ENSP00000364946	P1
MKX	ENST00000460919.2	c.103G>C	p.Asp35His	missense_variant	1/5	3		ENSP00000452751
MKX	ENST00000561227.1	c.103G>C	p.Asp35His	missense_variant	2/2	5		ENSP00000453746

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 05, 2023

The c.103G>C (p.D35H) alteration is located in exon 2 (coding exon 1) of the MKX gene. This alteration results from a G to C substitution at nucleotide position 103, causing the aspartic acid (D) at amino acid position 35 to be replaced by a histidine (H). 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	0.21
BayesDel_addAF	Uncertain	0.051	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.066	T;T;.;.
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.75	T;.;T;T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.26	T;T;T;T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	0.90	L;L;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.20	N;N;N;D
REVEL	Benign	0.19
Sift	Uncertain	0.022	D;D;D;D
Sift4G	Uncertain	0.030	D;D;.;D
Polyphen		0.98	D;D;.;.
Vest4		0.60
MutPred		0.18		Loss of solvent accessibility (P = 0.1473);Loss of solvent accessibility (P = 0.1473);Loss of solvent accessibility (P = 0.1473);Loss of solvent accessibility (P = 0.1473);
MVP		0.45
MPC		0.49
ClinPred		0.91	D
GERP RS		5.6
Varity_R		0.17
gMVP		0.58

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.

Other links and lift over

hg19: chr10-28032242;