chr10-27734625-C-A

Variant names:

• chr10-27734625-C-A
• rs1834709876
• NM_173576.3:c.669G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_173576.3(MKX):​c.669G>T​(p.Leu223Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MKX NM_173576.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.04
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173576.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MKX	NM_173576.3	MANE Select	c.669G>T	p.Leu223Phe	missense	Exon 5 of 7	NP_775847.2	Q8IYA7
	MKX	NM_001242702.2		c.669G>T	p.Leu223Phe	missense	Exon 5 of 7	NP_001229631.1	Q8IYA7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MKX	ENST00000419761.6	TSL:2 MANE Select	c.669G>T	p.Leu223Phe	missense	Exon 5 of 7	ENSP00000400896.1	Q8IYA7
	MKX	ENST00000375790.9	TSL:1	c.669G>T	p.Leu223Phe	missense	Exon 5 of 7	ENSP00000364946.4	Q8IYA7
	MKX	ENST00000969296.1		c.669G>T	p.Leu223Phe	missense	Exon 4 of 6	ENSP00000639355.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	MKX-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.31	T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.055	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Uncertain	0.14	D
MutationAssessor	Uncertain	2.0	M
PhyloP100		6.0
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.42
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.031	D
Polyphen		1.0	D
Vest4		0.80
MutPred		0.35		Gain of methylation at K219 (P = 0.0885)
MVP		0.52
MPC		0.59
ClinPred		0.98	D
GERP RS		5.6
Varity_R		0.39
gMVP		0.53
Mutation Taster		=25/75	disease causing

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

Other links and lift over

dbSNP: rs1834709876; hg19: chr10-28023554;