NM_173576.3:c.349-1468G>A

Variant names:

• chr10-27736842-C-T
• rs10508727
• NM_173576.3:c.349-1468G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
MKX	NM_173576.3	c.349-1468G>A		intron_variant	Intron 3 of 6	ENST00000419761.6	NP_775847.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MKX	ENST00000419761.6	c.349-1468G>A		intron_variant	Intron 3 of 6	2	NM_173576.3	ENSP00000400896.1
MKX	ENST00000375790.9	c.349-1468G>A		intron_variant	Intron 3 of 6	1		ENSP00000364946.4
MKX	ENST00000460919.2	c.349-1468G>A		intron_variant	Intron 2 of 4	3		ENSP00000452751.1

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

African (AFR) AF: 0.0146 AC: 604 AN: 41486

American (AMR) AF: 0.0325 AC: 496 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 354 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.0196 AC: 94 AN: 4808

European-Finnish (FIN) AF: 0.0592 AC: 624 AN: 10548

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0796 AC: 5410 AN: 67968

Other (OTH) AF: 0.0440 AC: 93 AN: 2112

Alfa AF: 0.0702 Hom.: 1771

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
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

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: rs10508727; hg19: chr10-28025771;