rs587781048

Positions:

• chr16-15745177-G-T
• chrNT_187607.1-1403188-G-T
• chr16-15745177-G-A
• chrNT_187607.1-1403188-G-A
• chr16-15745177-G-C
• chrNT_187607.1-1403188-G-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_002474.3(MYH11):​c.2472C>A​(p.Ala824Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,828 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 (★). Synonymous variant affecting the same amino acid position (i.e. A824A) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: MYH11 NM_002474.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.295

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]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 16-15745177-G-T is Benign according to our data. Variant chr16-15745177-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1155256.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.295 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH11	NM_002474.3	c.2472C>A	p.Ala824Ala	synonymous_variant	20/41	ENST00000300036.6	NP_002465.1
MYH11	NM_001040113.2	c.2493C>A	p.Ala831Ala	synonymous_variant	21/43	ENST00000452625.7	NP_001035202.1
MYH11	NM_001040114.2	c.2493C>A	p.Ala831Ala	synonymous_variant	21/42		NP_001035203.1
MYH11	NM_022844.3	c.2472C>A	p.Ala824Ala	synonymous_variant	20/42		NP_074035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH11	ENST00000300036.6	c.2472C>A	p.Ala824Ala	synonymous_variant	20/41	1	NM_002474.3	ENSP00000300036.5
MYH11	ENST00000452625.7	c.2493C>A	p.Ala831Ala	synonymous_variant	21/43	1	NM_001040113.2	ENSP00000407821.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461828 Hom.: 0 Cov.: 43 AF XY: 0.00000688 AC XY: 5 AN XY: 727210

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.0000497

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Aortic aneurysm, familial thoracic 4 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 24, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	3.7
DANN	Benign	0.85

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: rs1050113; hg19: chr16-15839034;