rs199798923
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate
The NM_002474.3(MYH11):c.5295+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000168 in 1,608,254 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000015 ( 0 hom. )
Consequence
MYH11
NM_002474.3 intron
NM_002474.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.651
Genes affected
MYH11 (HGNC:7569): (myosin heavy chain 11) The protein encoded by this gene is a smooth muscle myosin belonging to the myosin heavy chain family. The gene product is a subunit of a hexameric protein that consists of two heavy chain subunits and two pairs of non-identical light chain subunits. It functions as a major contractile protein, converting chemical energy into mechanical energy through the hydrolysis of ATP. A chromosomal rearrangement involving this gene is associated with acute myeloid leukemia of the M4Eo subtype. Mutations in this gene are associated with visceral myopathy, megacystis-microcolon-intestinal hypoperistalsis syndrome 2, and familial thoracic aortic aneurysm 4. [provided by RefSeq, May 2022]
NDE1 (HGNC:17619): (nudE neurodevelopment protein 1) This gene encodes a member of the nuclear distribution E (NudE) family of proteins. The encoded protein is localized at the centrosome and interacts with other centrosome components as part of a multiprotein complex that regulates dynein function. This protein plays an essential role in microtubule organization, mitosis and neuronal migration. Mutations in this gene cause lissencephaly 4, a disorder characterized by lissencephaly, severe brain atrophy, microcephaly, and severe cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2012]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
Variant 16-15718306-G-A is Benign according to our data. Variant chr16-15718306-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 534170.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYH11 | NM_001040113.2 | c.5316+9C>T | intron_variant | ENST00000452625.7 | NP_001035202.1 | |||
MYH11 | NM_002474.3 | c.5295+9C>T | intron_variant | ENST00000300036.6 | NP_002465.1 | |||
NDE1 | NM_017668.3 | c.948-5885G>A | intron_variant | ENST00000396354.6 | NP_060138.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYH11 | ENST00000300036.6 | c.5295+9C>T | intron_variant | 1 | NM_002474.3 | ENSP00000300036 | P3 | |||
NDE1 | ENST00000396354.6 | c.948-5885G>A | intron_variant | 1 | NM_017668.3 | ENSP00000379642 | P1 | |||
MYH11 | ENST00000452625.7 | c.5316+9C>T | intron_variant | 1 | NM_001040113.2 | ENSP00000407821 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152134Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000162 AC: 4AN: 247314Hom.: 0 AF XY: 0.00000746 AC XY: 1AN XY: 134078
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GnomAD4 exome AF: 0.0000151 AC: 22AN: 1456002Hom.: 0 Cov.: 31 AF XY: 0.0000152 AC XY: 11AN XY: 724546
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GnomAD4 genome AF: 0.0000328 AC: 5AN: 152252Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74436
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Aortic aneurysm, familial thoracic 4 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 10, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at