chr16-15703571-G-C

Position:

• chr16-15703571-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002474.3(MYH11):​c.*420C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0336 in 340,898 control chromosomes in the GnomAD database, including 302 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.038 (153 hom., cov: 32)
  • Exomes 𝑓: 0.030 (149 hom.)
• Consequence: MYH11 NM_002474.3 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0680

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 16-15703571-G-C is Benign according to our data. Variant chr16-15703571-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 318081.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH11	NM_001040113.2	c.*561C>G		3_prime_UTR_variant	43/43	ENST00000452625.7	NP_001035202.1
MYH11	NM_002474.3	c.*420C>G		3_prime_UTR_variant	41/41	ENST00000300036.6	NP_002465.1
NDE1	NM_017668.3	c.947+6711G>C		intron_variant		ENST00000396354.6	NP_060138.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH11	ENST00000300036.6	c.*420C>G		3_prime_UTR_variant	41/41	1	NM_002474.3	ENSP00000300036	P3
MYH11	ENST00000452625.7	c.*561C>G		3_prime_UTR_variant	43/43	1	NM_001040113.2	ENSP00000407821
NDE1	ENST00000396354.6	c.947+6711G>C		intron_variant		1	NM_017668.3	ENSP00000379642	P1

Frequencies

GnomAD3 genomes AF: 0.0378 AC: 5750 AN: 152066 Hom.: 148 Cov.: 32

Gnomad AFR AF: 0.0542

Gnomad AMI AF: 0.0956

Gnomad AMR AF: 0.0328

Gnomad ASJ AF: 0.0262

Gnomad EAS AF: 0.00808

Gnomad SAS AF: 0.0918

Gnomad FIN AF: 0.0312

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0283

Gnomad OTH AF: 0.0387

GnomAD4 exome AF: 0.0301 AC: 5676 AN: 188714 Hom.: 149 Cov.: 0 AF XY: 0.0334 AC XY: 3181 AN XY: 95122

Gnomad4 AFR exome AF: 0.0530

Gnomad4 AMR exome AF: 0.0188

Gnomad4 ASJ exome AF: 0.0238

Gnomad4 EAS exome AF: 0.00731

Gnomad4 SAS exome AF: 0.0718

Gnomad4 FIN exome AF: 0.0291

Gnomad4 NFE exome AF: 0.0264

Gnomad4 OTH exome AF: 0.0305

GnomAD4 genome AF: 0.0380 AC: 5781 AN: 152184 Hom.: 153 Cov.: 32 AF XY: 0.0395 AC XY: 2940 AN XY: 74382

Gnomad4 AFR AF: 0.0544

Gnomad4 AMR AF: 0.0327

Gnomad4 ASJ AF: 0.0262

Gnomad4 EAS AF: 0.00810

Gnomad4 SAS AF: 0.0930

Gnomad4 FIN AF: 0.0312

Gnomad4 NFE AF: 0.0283

Gnomad4 OTH AF: 0.0449

Alfa AF: 0.0343 Hom.: 8

Bravo AF: 0.0363

Asia WGS AF: 0.0570 AC: 197 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Familial thoracic aortic aneurysm and aortic dissection Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Lissencephaly 4 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Aortic aneurysm, familial thoracic 4 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.85
DANN	Benign	0.44

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

Other links and lift over

dbSNP: rs12932063; hg19: chr16-15797428;