17-43642032-C-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004527.4(MEOX1):c.643G>A(p.Val215Ile) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,612,414 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000027 ( 0 hom. )
Consequence
MEOX1
NM_004527.4 missense, splice_region
NM_004527.4 missense, splice_region
Scores
6
3
7
Splicing: ADA: 0.9639
1
1
Clinical Significance
Conservation
PhyloP100: 7.26
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MEOX1 | NM_004527.4 | c.643G>A | p.Val215Ile | missense_variant, splice_region_variant | 3/3 | ENST00000318579.9 | |
MEOX1 | NM_013999.4 | c.470G>A | p.Gly157Asp | missense_variant, splice_region_variant | 2/2 | ||
MEOX1 | NM_001040002.2 | c.298G>A | p.Val100Ile | missense_variant, splice_region_variant | 4/4 | ||
MEOX1 | XM_011524818.3 | c.654G>A | p.Arg218= | splice_region_variant, synonymous_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MEOX1 | ENST00000318579.9 | c.643G>A | p.Val215Ile | missense_variant, splice_region_variant | 3/3 | 1 | NM_004527.4 | P1 | |
MEOX1 | ENST00000549132.2 | c.470G>A | p.Gly157Asp | missense_variant, splice_region_variant | 2/2 | 1 | |||
MEOX1 | ENST00000393661.2 | c.298G>A | p.Val100Ile | missense_variant, splice_region_variant | 4/4 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152142Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000202 AC: 5AN: 247344Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 133862
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GnomAD4 exome AF: 0.0000267 AC: 39AN: 1460272Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 18AN XY: 726388
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152142Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74322
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 28, 2024 | The c.643G>A (p.V215I) alteration is located in exon 3 (coding exon 3) of the MEOX1 gene. This alteration results from a G to A substitution at nucleotide position 643, causing the valine (V) at amino acid position 215 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Uncertain
T
MetaSVM
Pathogenic
D
MutationTaster
Benign
D;D;D;D
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Vest4
MutPred
Loss of sheet (P = 0.0181);
MVP
ClinPred
D
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at