rs10508727

Positions:

• chr10-27736842-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173576.3(MKX):​c.349-1468G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0508 in 152,046 control chromosomes in the GnomAD database, including 269 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.051 (269 hom., cov: 32)
• Consequence: MKX NM_173576.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.135

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MKX	NM_173576.3	c.349-1468G>A		intron_variant		ENST00000419761.6	NP_775847.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MKX	ENST00000419761.6	c.349-1468G>A		intron_variant		2	NM_173576.3	ENSP00000400896	P1
MKX	ENST00000375790.9	c.349-1468G>A		intron_variant		1		ENSP00000364946	P1
MKX	ENST00000460919.2	c.349-1468G>A		intron_variant		3		ENSP00000452751

Frequencies

GnomAD3 genomes AF: 0.0508 AC: 7724 AN: 151928 Hom.: 269 Cov.: 32

Gnomad AFR AF: 0.0146

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0325

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0193

Gnomad FIN AF: 0.0592

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0796

Gnomad OTH AF: 0.0445

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0508 AC: 7724 AN: 152046 Hom.: 269 Cov.: 32 AF XY: 0.0482 AC XY: 3585 AN XY: 74324

Gnomad4 AFR AF: 0.0146

Gnomad4 AMR AF: 0.0325

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0196

Gnomad4 FIN AF: 0.0592

Gnomad4 NFE AF: 0.0796

Gnomad4 OTH AF: 0.0440

Alfa AF: 0.0724 Hom.: 892

Bravo AF: 0.0476

Asia WGS AF: 0.0110 AC: 37 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.4
DANN	Benign	0.59

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

Other links and lift over

dbSNP: rs10508727; hg19: chr10-28025771;