7-15686305-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_005924.5(MEOX2):​c.98C>G​(p.Ser33Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

MEOX2
NM_005924.5 missense

Scores

6
6
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.62
Variant links:
Genes affected
MEOX2 (HGNC:7014): (mesenchyme homeobox 2) 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 regulation of vertebrate limb myogenesis. Mutations in the related mouse protein may be associated with craniofacial and/or skeletal abnormalities, in addition to neurovascular dysfunction observed in Alzheimer's disease. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.809

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MEOX2NM_005924.5 linkuse as main transcriptc.98C>G p.Ser33Cys missense_variant 1/3 ENST00000262041.6 NP_005915.2 P50222

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MEOX2ENST00000262041.6 linkuse as main transcriptc.98C>G p.Ser33Cys missense_variant 1/31 NM_005924.5 ENSP00000262041.5 P50222

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
39
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 04, 2024The c.98C>G (p.S33C) alteration is located in exon 1 (coding exon 1) of the MEOX2 gene. This alteration results from a C to G substitution at nucleotide position 98, causing the serine (S) at amino acid position 33 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.20
BayesDel_addAF
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.16
CADD
Pathogenic
26
DANN
Uncertain
0.98
DEOGEN2
Benign
0.16
T
Eigen
Pathogenic
0.71
Eigen_PC
Pathogenic
0.69
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.88
D
M_CAP
Uncertain
0.11
D
MetaRNN
Pathogenic
0.81
D
MetaSVM
Uncertain
0.72
D
MutationAssessor
Benign
1.8
L
PrimateAI
Pathogenic
0.80
D
PROVEAN
Benign
-0.83
N
REVEL
Uncertain
0.64
Sift
Benign
0.075
T
Sift4G
Benign
0.098
T
Polyphen
0.99
D
Vest4
0.80
MutPred
0.32
Loss of phosphorylation at S33 (P = 0.028);
MVP
0.75
MPC
0.52
ClinPred
0.97
D
GERP RS
4.5
Varity_R
0.23
gMVP
0.45

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-15725930; API