rs727504230

Variant names:

• chr17-8513561-C-A
• rs727504230
• NM_001256012.3:c.2722G>T

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_001256012.3(MYH10):​c.2722G>T​(p.Glu908*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYH10 NM_001256012.3 stop_gained
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 7.91
• Publications: 5 publications found

Genes affected

MYH10 (HGNC:7568): (myosin heavy chain 10) This gene encodes a member of the myosin superfamily. The protein represents a conventional non-muscle myosin; it should not be confused with the unconventional myosin-10 (MYO10). Myosins are actin-dependent motor proteins with diverse functions including regulation of cytokinesis, cell motility, and cell polarity. Mutations in this gene have been associated with May-Hegglin anomaly and developmental defects in brain and heart. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

MYH10 Gene-Disease associations (from GenCC):

• MYH10-related neurodevelopmental disorder with congenital anomalies

  Inheritance: AD Classification: MODERATE Submitted by: G2P
• coloboma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

LOC102724262 (HGNC:):

ACMG classification

Our verdict: Pathogenic. The variant received 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256012.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH10	NM_001256012.3	MANE Select	c.2722G>T	p.Glu908*	stop_gained	Exon 23 of 43	NP_001242941.1
	MYH10	NM_001375266.1		c.2659G>T	p.Glu887*	stop_gained	Exon 22 of 42	NP_001362195.1
	MYH10	NM_001256095.2		c.2656G>T	p.Glu886*	stop_gained	Exon 22 of 42	NP_001243024.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH10	ENST00000360416.8	TSL:1 MANE Select	c.2722G>T	p.Glu908*	stop_gained	Exon 23 of 43	ENSP00000353590.4
	MYH10	ENST00000379980.8	TSL:1	c.2656G>T	p.Glu886*	stop_gained	Exon 22 of 42	ENSP00000369315.5
	MYH10	ENST00000269243.8	TSL:1	c.2629G>T	p.Glu877*	stop_gained	Exon 21 of 41	ENSP00000269243.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:1

Dec 01, 2014

OMIM

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Pathogenic	0.66
CADD	Pathogenic	42
DANN	Uncertain	1.0
Eigen	Pathogenic	1.2
Eigen_PC	Pathogenic	1.0
FATHMM_MKL	Pathogenic	0.99	D
PhyloP100		7.9
Vest4		0.87
GERP RS		5.1
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7
Mutation Taster		=1/199	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs727504230; hg19: chr17-8416879;