chr17-10447129-T-G
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_017533.2(MYH4):āc.5053A>Cā(p.Met1685Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,614,026 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_017533.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH4 | NM_017533.2 | c.5053A>C | p.Met1685Leu | missense_variant | 35/40 | ENST00000255381.2 | |
MYHAS | NR_125367.1 | n.167+40891T>G | intron_variant, non_coding_transcript_variant | ||||
MYH4 | XM_017024676.2 | c.5053A>C | p.Met1685Leu | missense_variant | 33/38 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH4 | ENST00000255381.2 | c.5053A>C | p.Met1685Leu | missense_variant | 35/40 | 1 | NM_017533.2 | P1 | |
ENST00000399342.6 | n.206+40852T>G | intron_variant, non_coding_transcript_variant | 3 | ||||||
ENST00000581304.1 | n.143+40891T>G | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152172Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251444Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135896
GnomAD4 exome AF: 0.0000205 AC: 30AN: 1461854Hom.: 1 Cov.: 31 AF XY: 0.0000234 AC XY: 17AN XY: 727230
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152172Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74344
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 09, 2023 | The c.5053A>C (p.M1685L) alteration is located in exon 35 (coding exon 33) of the MYH4 gene. This alteration results from a A to C substitution at nucleotide position 5053, causing the methionine (M) at amino acid position 1685 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at