chr17-10443494-G-A
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_017533.2(MYH4):c.5701C>T(p.Arg1901Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000154 in 1,613,936 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00025 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00014 ( 0 hom. )
Consequence
MYH4
NM_017533.2 missense
NM_017533.2 missense
Scores
11
5
3
Clinical Significance
Conservation
PhyloP100: 1.40
Genes affected
MYH4 (HGNC:7574): (myosin heavy chain 4) Enables double-stranded RNA binding activity. Involved in muscle contraction. Located in myofibril. [provided by Alliance of Genome Resources, Apr 2022]
MYHAS (HGNC:50609): (myosin heavy chain gene cluster antisense RNA) Predicted to enable primary miRNA binding activity. Predicted to be involved in response to muscle activity and skeletal muscle fiber development. Predicted to act upstream of or within with a positive effect on gene expression. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAd4 at 38 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYH4 | NM_017533.2 | c.5701C>T | p.Arg1901Cys | missense_variant | 40/40 | ENST00000255381.2 | NP_060003.2 | |
MYH4 | XM_017024676.2 | c.5701C>T | p.Arg1901Cys | missense_variant | 38/38 | XP_016880165.1 | ||
MYHAS | NR_125367.1 | n.167+37256G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYH4 | ENST00000255381.2 | c.5701C>T | p.Arg1901Cys | missense_variant | 40/40 | 1 | NM_017533.2 | ENSP00000255381.2 | ||
ENSG00000272736 | ENST00000399342.6 | n.206+37217G>A | intron_variant | 3 | ||||||
ENSG00000272736 | ENST00000581304.1 | n.143+37256G>A | intron_variant | 3 | ||||||
MYHAS | ENST00000587182.2 | n.155+37256G>A | intron_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.000230 AC: 35AN: 152162Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000334 AC: 84AN: 251336Hom.: 0 AF XY: 0.000309 AC XY: 42AN XY: 135844
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GnomAD4 exome AF: 0.000144 AC: 210AN: 1461656Hom.: 0 Cov.: 31 AF XY: 0.000142 AC XY: 103AN XY: 727124
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GnomAD4 genome AF: 0.000250 AC: 38AN: 152280Hom.: 1 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74460
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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 submitter | clinical testing | Ambry Genetics | Nov 07, 2022 | The c.5701C>T (p.R1901C) alteration is located in exon 40 (coding exon 38) of the MYH4 gene. This alteration results from a C to T substitution at nucleotide position 5701, causing the arginine (R) at amino acid position 1901 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Uncertain
T
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
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