chr15-89750712-T-C
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_018670.4(MESP1):c.520A>G(p.Met174Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00227 in 1,385,834 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.012 ( 39 hom., cov: 34)
Exomes 𝑓: 0.0011 ( 28 hom. )
Consequence
MESP1
NM_018670.4 missense
NM_018670.4 missense
Scores
1
17
Clinical Significance
Conservation
PhyloP100: -0.622
Genes affected
MESP1 (HGNC:29658): (mesoderm posterior bHLH transcription factor 1) Enables DNA-binding transcription factor activity and transcription cis-regulatory region binding activity. Involved in several processes, including endothelial cell differentiation; heart development; and positive regulation of transcription by RNA polymerase II. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
?
Variant 15-89750712-T-C is Benign according to our data. Variant chr15-89750712-T-C is described in ClinVar as [Benign]. Clinvar id is 1537845.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0118 (1791/152244) while in subpopulation AFR AF= 0.0411 (1707/41572). AF 95% confidence interval is 0.0394. There are 39 homozygotes in gnomad4. There are 878 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 39 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MESP1 | NM_018670.4 | c.520A>G | p.Met174Val | missense_variant | 1/2 | ENST00000300057.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MESP1 | ENST00000300057.5 | c.520A>G | p.Met174Val | missense_variant | 1/2 | 1 | NM_018670.4 | P1 | |
MESP1 | ENST00000559894.1 | n.114+312A>G | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0118 AC: 1790AN: 152136Hom.: 39 Cov.: 34
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GnomAD3 exomes AF: 0.00280 AC: 122AN: 43542Hom.: 2 AF XY: 0.00215 AC XY: 54AN XY: 25156
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GnomAD4 exome AF: 0.00109 AC: 1350AN: 1233590Hom.: 28 Cov.: 66 AF XY: 0.000925 AC XY: 554AN XY: 598984
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
MESP1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 19, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 02, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
N
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
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
DS_DG_spliceai
Position offset: 1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at