rs62636562
Positions:
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_002448.3(MSX1):c.821C>T(p.Ala274Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000466 in 1,608,454 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.00029 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000021 ( 0 hom. )
Consequence
MSX1
NM_002448.3 missense
NM_002448.3 missense
Scores
10
9
Clinical Significance
Conservation
PhyloP100: 5.96
Genes affected
MSX1 (HGNC:7391): (msh homeobox 1) This gene encodes a member of the muscle segment homeobox gene family. The encoded protein functions as a transcriptional repressor during embryogenesis through interactions with components of the core transcription complex and other homeoproteins. It may also have roles in limb-pattern formation, craniofacial development, particularly odontogenesis, and tumor growth inhibition. Mutations in this gene, which was once known as homeobox 7, have been associated with nonsyndromic cleft lip with or without cleft palate 5, Witkop syndrome, Wolf-Hirschom syndrome, and autosomoal dominant hypodontia. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.05887142).
BP6
?
Variant 4-4863052-C-T is Benign according to our data. Variant chr4-4863052-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 800248.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000289 (44/152328) while in subpopulation AFR AF= 0.00106 (44/41576). AF 95% confidence interval is 0.000809. There are 0 homozygotes in gnomad4. There are 21 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 44 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MSX1 | NM_002448.3 | c.821C>T | p.Ala274Val | missense_variant | 2/2 | ENST00000382723.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MSX1 | ENST00000382723.5 | c.821C>T | p.Ala274Val | missense_variant | 2/2 | 1 | NM_002448.3 | P1 | |
MSX1 | ENST00000468421.1 | downstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000289 AC: 44AN: 152210Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000956 AC: 22AN: 230128Hom.: 0 AF XY: 0.0000550 AC XY: 7AN XY: 127334
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GnomAD4 exome AF: 0.0000213 AC: 31AN: 1456126Hom.: 0 Cov.: 34 AF XY: 0.0000180 AC XY: 13AN XY: 724074
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GnomAD4 genome ? AF: 0.000289 AC: 44AN: 152328Hom.: 0 Cov.: 33 AF XY: 0.000282 AC XY: 21AN XY: 74482
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hypoplastic enamel-onycholysis-hypohidrosis syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 28, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Uncertain
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at