Variant 17-43641962-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_004527.4(MEOX1):c.713A>G(p.Asn238Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000231 in 1,613,918 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 3 hom. )

Consequence

MEOX1
NM_004527.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.593

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004714489).

BP6

Variant 17-43641962-T-C is Benign according to our data. Variant chr17-43641962-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 714734.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MEOX1	NM_004527.4 linkuse as main transcript	c.713A>G	p.Asn238Ser	missense_variant	3/3	ENST00000318579.9
MEOX1	NM_001040002.2 linkuse as main transcript	c.368A>G	p.Asn123Ser	missense_variant	4/4
MEOX1	NM_013999.4 linkuse as main transcript	c.540A>G	p.Gln180=	synonymous_variant	2/2
MEOX1	XM_011524818.3 linkuse as main transcript	c.*40A>G		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEOX1	ENST00000318579.9 linkuse as main transcript	c.713A>G	p.Asn238Ser	missense_variant	3/3	1	NM_004527.4	P1	P50221-1
MEOX1	ENST00000549132.2 linkuse as main transcript	c.540A>G	p.Gln180=	synonymous_variant	2/2	1			P50221-2
MEOX1	ENST00000393661.2 linkuse as main transcript	c.368A>G	p.Asn123Ser	missense_variant	4/4	3			P50221-3

Frequencies

GnomAD3 genomes

AF:

0.00106

AC:

161

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00343

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000412

AC:

103

AN:

249774

Hom.:

AF XY:

0.000318

AC XY:

AN XY:

135132

show subpopulations

Gnomad AFR exome

AF:

0.00375

Gnomad AMR exome

AF:

0.000723

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.0000624

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000145

AC:

212

AN:

1461694

Hom.:

Cov.:

AF XY:

0.000127

AC XY:

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.00299

Gnomad4 AMR exome

AF:

0.000738

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000197

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000351

Gnomad4 OTH exome

AF:

0.000364

GnomAD4 genome

AF:

0.00106

AC:

161

AN:

152224

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00342

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000286

Hom.:

Bravo

AF:

0.00125

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00340

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000404

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

MEOX1-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 16, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 19, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.49

CADD

Benign

0.25

DANN

Benign

0.44

DEOGEN2

Benign

0.029

T;T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.059

T;T;T

M_CAP

Benign

0.030

MetaRNN

Benign

0.0047

T;T;T

MetaSVM

Benign

-0.73

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

0.0

N;N;N

REVEL

Benign

0.14

Sift

Benign

0.42

T;D;T

Sift4G

Benign

0.42

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.034

MVP

0.84

MPC

0.081

ClinPred

0.0016

GERP RS

1.1

Varity_R

0.019

gMVP

0.20

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