rs12532
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_002448.3(MSX1):c.*276A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 457,632 control chromosomes in the GnomAD database, including 28,816 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.36 ( 10750 hom., cov: 28)
Exomes 𝑓: 0.33 ( 18066 hom. )
Consequence
MSX1
NM_002448.3 3_prime_UTR
NM_002448.3 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.07
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 4-4863419-A-G is Benign according to our data. Variant chr4-4863419-A-G is described in ClinVar as [Benign]. Clinvar id is 530788.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.363 AC: 54985AN: 151446Hom.: 10724 Cov.: 28
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GnomAD4 exome AF: 0.329 AC: 100810AN: 306068Hom.: 18066 Cov.: 0 AF XY: 0.325 AC XY: 52071AN XY: 160186
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GnomAD4 genome AF: 0.363 AC: 55071AN: 151564Hom.: 10750 Cov.: 28 AF XY: 0.370 AC XY: 27397AN XY: 74032
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 19, 2021 | This variant is associated with the following publications: (PMID: 23549991, 23231047, 24603642) - |
Hypoplastic enamel-onycholysis-hypohidrosis syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 06, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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