16-15703925-GTTTTT-GT
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1
The NM_002474.3(MYH11):c.*62_*65delAAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000996 in 1,606,350 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000089 ( 1 hom. )
Consequence
MYH11
NM_002474.3 3_prime_UTR
NM_002474.3 3_prime_UTR
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.27
Publications
1 publications found
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]
NDE1 Gene-Disease associations (from GenCC):
- lissencephaly 4Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: PanelApp Australia, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
- hydranencephalyInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- microlissencephalyInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- NDE1-related microhydranencephalyInheritance: Unknown, AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -4 ACMG points.
BS1
Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.00000894 (13/1454660) while in subpopulation AMR AF = 0.000157 (7/44674). AF 95% confidence interval is 0.0000729. There are 1 homozygotes in GnomAdExome4. There are 6 alleles in the male GnomAdExome4 subpopulation. This position passed quality control check.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYH11 | NM_002474.3 | c.*62_*65delAAAA | 3_prime_UTR_variant | Exon 41 of 41 | ENST00000300036.6 | NP_002465.1 | ||
MYH11 | NM_001040113.2 | c.*203_*206delAAAA | 3_prime_UTR_variant | Exon 43 of 43 | ENST00000452625.7 | NP_001035202.1 | ||
NDE1 | NM_017668.3 | c.947+7070_947+7073delTTTT | intron_variant | Intron 8 of 8 | ENST00000396354.6 | NP_060138.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYH11 | ENST00000300036.6 | c.*62_*65delAAAA | 3_prime_UTR_variant | Exon 41 of 41 | 1 | NM_002474.3 | ENSP00000300036.5 | |||
MYH11 | ENST00000452625.7 | c.*203_*206delAAAA | 3_prime_UTR_variant | Exon 43 of 43 | 1 | NM_001040113.2 | ENSP00000407821.2 | |||
NDE1 | ENST00000396354.6 | c.947+7070_947+7073delTTTT | intron_variant | Intron 8 of 8 | 1 | NM_017668.3 | ENSP00000379642.1 |
Frequencies
GnomAD3 genomes AF: 0.0000198 AC: 3AN: 151690Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
3
AN:
151690
Hom.:
Cov.:
32
Gnomad AFR
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Gnomad FIN
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Gnomad NFE
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Gnomad OTH
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GnomAD2 exomes AF: 0.0000360 AC: 9AN: 249778 AF XY: 0.0000296 show subpopulations
GnomAD2 exomes
AF:
AC:
9
AN:
249778
AF XY:
Gnomad AFR exome
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GnomAD4 exome AF: 0.00000894 AC: 13AN: 1454660Hom.: 1 AF XY: 0.00000829 AC XY: 6AN XY: 724022 show subpopulations
GnomAD4 exome
AF:
AC:
13
AN:
1454660
Hom.:
AF XY:
AC XY:
6
AN XY:
724022
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33326
American (AMR)
AF:
AC:
7
AN:
44674
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26078
East Asian (EAS)
AF:
AC:
1
AN:
39578
South Asian (SAS)
AF:
AC:
0
AN:
85804
European-Finnish (FIN)
AF:
AC:
0
AN:
53040
Middle Eastern (MID)
AF:
AC:
0
AN:
5676
European-Non Finnish (NFE)
AF:
AC:
3
AN:
1106390
Other (OTH)
AF:
AC:
2
AN:
60094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.520
Heterozygous variant carriers
0
1
2
2
3
4
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Allele balance
GnomAD4 genome AF: 0.0000198 AC: 3AN: 151690Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74084 show subpopulations
GnomAD4 genome
AF:
AC:
3
AN:
151690
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74084
show subpopulations
African (AFR)
AF:
AC:
2
AN:
41214
American (AMR)
AF:
AC:
0
AN:
15212
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5178
South Asian (SAS)
AF:
AC:
0
AN:
4790
European-Finnish (FIN)
AF:
AC:
0
AN:
10546
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
1
AN:
67964
Other (OTH)
AF:
AC:
0
AN:
2088
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
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
Publications
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