16-15703972-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1

The NM_002474.3(MYH11):​c.*19G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00022 in 1,613,786 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00023 ( 1 hom. )

Consequence

MYH11
NM_002474.3 3_prime_UTR

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.768
Variant links:
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 Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 16-15703972-C-T is Benign according to our data. Variant chr16-15703972-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 381045.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000171 (26/152052) while in subpopulation NFE AF= 0.000235 (16/67990). AF 95% confidence interval is 0.000147. There are 0 homozygotes in gnomad4. There are 14 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MYH11NM_002474.3 linkc.*19G>A 3_prime_UTR_variant Exon 41 of 41 ENST00000300036.6 NP_002465.1 P35749-1A0A024QZJ4
MYH11NM_001040113.2 linkc.*160G>A 3_prime_UTR_variant Exon 43 of 43 ENST00000452625.7 NP_001035202.1 P35749-3
NDE1NM_017668.3 linkc.947+7112C>T intron_variant Intron 8 of 8 ENST00000396354.6 NP_060138.1 Q9NXR1-2X5DR54

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MYH11ENST00000300036 linkc.*19G>A 3_prime_UTR_variant Exon 41 of 41 1 NM_002474.3 ENSP00000300036.5 P35749-1
MYH11ENST00000452625 linkc.*160G>A 3_prime_UTR_variant Exon 43 of 43 1 NM_001040113.2 ENSP00000407821.2 P35749-3
NDE1ENST00000396354.6 linkc.947+7112C>T intron_variant Intron 8 of 8 1 NM_017668.3 ENSP00000379642.1 Q9NXR1-2

Frequencies

GnomAD3 genomes
AF:
0.000171
AC:
26
AN:
151934
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000946
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000235
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000239
AC:
60
AN:
251484
Hom.:
0
AF XY:
0.000243
AC XY:
33
AN XY:
135918
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00166
Gnomad NFE exome
AF:
0.000185
Gnomad OTH exome
AF:
0.000489
GnomAD4 exome
AF:
0.000225
AC:
329
AN:
1461734
Hom.:
1
Cov.:
31
AF XY:
0.000230
AC XY:
167
AN XY:
727158
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00193
Gnomad4 NFE exome
AF:
0.000191
Gnomad4 OTH exome
AF:
0.000232
GnomAD4 genome
AF:
0.000171
AC:
26
AN:
152052
Hom.:
0
Cov.:
32
AF XY:
0.000188
AC XY:
14
AN XY:
74318
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000946
Gnomad4 NFE
AF:
0.000235
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000476
Hom.:
0
Bravo
AF:
0.0000567

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxOct 12, 2015This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
2.3
DANN
Benign
0.79

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs187644296; hg19: chr16-15797829; API