17-10309527-G-A
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_003802.3(MYH13):c.4960C>T(p.Leu1654Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000168 in 1,605,802 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00098 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000083 ( 0 hom. )
Consequence
MYH13
NM_003802.3 missense
NM_003802.3 missense
Scores
1
5
9
Clinical Significance
Conservation
PhyloP100: 5.65
Genes affected
MYH13 (HGNC:7571): (myosin heavy chain 13) Predicted to enable microfilament motor activity. Predicted to be involved in muscle contraction. Predicted to act upstream of or within cellular response to starvation. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.033980697).
BP6
?
Variant 17-10309527-G-A is Benign according to our data. Variant chr17-10309527-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2225358.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BS2
?
High AC in GnomAd at 145 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH13 | NM_003802.3 | c.4960C>T | p.Leu1654Phe | missense_variant | 34/41 | ENST00000252172.9 | |
LOC107985004 | XR_007065617.1 | n.96-7971G>A | intron_variant, non_coding_transcript_variant | ||||
LOC107985004 | XR_001752791.3 | n.96-7971G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH13 | ENST00000252172.9 | c.4960C>T | p.Leu1654Phe | missense_variant | 34/41 | 1 | NM_003802.3 | P1 | |
MYH13 | ENST00000621918.1 | c.4960C>T | p.Leu1654Phe | missense_variant | 32/39 | 1 | P1 | ||
ENST00000609088.1 | n.95-7971G>A | intron_variant, non_coding_transcript_variant | 4 | ||||||
MYH13 | ENST00000418404.8 | c.4960C>T | p.Leu1654Phe | missense_variant | 33/40 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000952 AC: 145AN: 152260Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000157 AC: 38AN: 241722Hom.: 0 AF XY: 0.000129 AC XY: 17AN XY: 131278
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GnomAD4 exome AF: 0.0000826 AC: 120AN: 1453424Hom.: 0 Cov.: 31 AF XY: 0.0000873 AC XY: 63AN XY: 721926
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GnomAD4 genome ? AF: 0.000978 AC: 149AN: 152378Hom.: 0 Cov.: 33 AF XY: 0.00103 AC XY: 77AN XY: 74508
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 08, 2022 | The c.4960C>T (p.L1654F) alteration is located in exon 34 (coding exon 32) of the MYH13 gene. This alteration results from a C to T substitution at nucleotide position 4960, causing the leucine (L) at amino acid position 1654 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
MYH13-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 05, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Uncertain
D;D;D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;M;M
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
Sift4G
Benign
T;T;T
Polyphen
B;B;B
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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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