Variant chr17-43642011-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5

The NM_004527.4(MEOX1):c.664C>T(p.Arg222Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,608 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

MEOX1
NM_004527.4 stop_gained

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 2.04

Variant links:

Genes affected

MEOX1 (HGNC:7013): (mesenchyme homeobox 1) This gene encodes a member of a subfamily of non-clustered, diverged, antennapedia-like homeobox-containing genes. The encoded protein may play a role in the molecular signaling network regulating somite development. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

MEOX1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.132 CDS is truncated, and there are 1 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 17-43642011-G-A is Pathogenic according to our data. Variant chr17-43642011-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 39508.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-43642011-G-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MEOX1	NM_004527.4 linkuse as main transcript	c.664C>T	p.Arg222Ter	stop_gained	3/3	ENST00000318579.9	NP_004518.1
MEOX1	NM_001040002.2 linkuse as main transcript	c.319C>T	p.Arg107Ter	stop_gained	4/4		NP_001035091.1
MEOX1	NM_013999.4 linkuse as main transcript	c.491C>T	p.Pro164Leu	missense_variant	2/2		NP_054705.1
MEOX1	XM_011524818.3 linkuse as main transcript	c.675C>T	p.Thr225=	synonymous_variant	3/3		XP_011523120.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEOX1	ENST00000318579.9 linkuse as main transcript	c.664C>T	p.Arg222Ter	stop_gained	3/3	1	NM_004527.4	ENSP00000321684	P1	P50221-1
MEOX1	ENST00000549132.2 linkuse as main transcript	c.491C>T	p.Pro164Leu	missense_variant	2/2	1		ENSP00000449049		P50221-2
MEOX1	ENST00000393661.2 linkuse as main transcript	c.319C>T	p.Arg107Ter	stop_gained	4/4	3		ENSP00000377271		P50221-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248836

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134714

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000898

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461608

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727134

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:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Klippel-Feil syndrome 2, autosomal recessive

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 10, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.63

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.55

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;D;D;D

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.19

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.013

Vest4

0.24

MutPred

0.11

Loss of loop (P = 0.0128);

MVP

0.76

ClinPred

1.0

GERP RS

3.6

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over