16-15703925-G-GT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002474.3(MYH11):c.*65_*66insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00498 in 1,606,278 control chromosomes in the GnomAD database, including 333 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.027 (178 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (155 hom.)
• Consequence: MYH11 NM_002474.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.794

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 -10 ACMG points.

• BP6: Variant 16-15703925-G-GT is Benign according to our data. Variant chr16-15703925-G-GT is described in ClinVar as [Benign]. Clinvar id is 1294395.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH11	NM_001040113.2	c.*206_*207insA		3_prime_UTR_variant	43/43	ENST00000452625.7
MYH11	NM_002474.3	c.*65_*66insA		3_prime_UTR_variant	41/41	ENST00000300036.6
NDE1	NM_017668.3	c.947+7073dup		intron_variant		ENST00000396354.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH11	ENST00000300036.6	c.*65_*66insA		3_prime_UTR_variant	41/41	1	NM_002474.3	P3
MYH11	ENST00000452625.7	c.*206_*207insA		3_prime_UTR_variant	43/43	1	NM_001040113.2
NDE1	ENST00000396354.6	c.947+7073dup		intron_variant		1	NM_017668.3	P1

Frequencies

GnomAD3 genomes AF: 0.0270 AC: 4098 AN: 151678 Hom.: 178 Cov.: 32

Gnomad AFR AF: 0.0948

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00933

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0168

GnomAD3 exomes AF: 0.00697 AC: 1742 AN: 249778 Hom.: 78 AF XY: 0.00520 AC XY: 703 AN XY: 135118

Gnomad AFR exome AF: 0.0952

Gnomad AMR exome AF: 0.00489

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000168

Gnomad OTH exome AF: 0.00197

GnomAD4 exome AF: 0.00267 AC: 3889 AN: 1454482 Hom.: 155 Cov.: 30 AF XY: 0.00226 AC XY: 1634 AN XY: 723972

Gnomad4 AFR exome AF: 0.0929

Gnomad4 AMR exome AF: 0.00537

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.000303

Gnomad4 FIN exome AF: 0.0000189

Gnomad4 NFE exome AF: 0.000136

Gnomad4 OTH exome AF: 0.00598

GnomAD4 genome AF: 0.0271 AC: 4110 AN: 151796 Hom.: 178 Cov.: 32 AF XY: 0.0257 AC XY: 1905 AN XY: 74206

Gnomad4 AFR AF: 0.0949

Gnomad4 AMR AF: 0.00926

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.0166

Bravo AF: 0.0311

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 11, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs5815842; hg19: chr16-15797782;