19-50289926-C-G

Variant names:

• chr19-50289926-C-G
• rs588035
• NM_001145809.2:c.4965+278C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001145809.2(MYH14):​c.4965+278C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 151,810 control chromosomes in the GnomAD database, including 35,607 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.67 (35607 hom., cov: 29)
• Consequence: MYH14 NM_001145809.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.424
• Publications: 8 publications found

Genes affected

MYH14 (HGNC:23212): (myosin heavy chain 14) 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-14 (MYO14). Myosins are actin-dependent motor proteins with diverse functions including regulation of cytokinesis, cell motility, and cell polarity. Mutations in this gene result in one form of autosomal dominant hearing impairment. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

MYH14 Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss 4A

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 19-50289926-C-G is Benign according to our data. Variant chr19-50289926-C-G is described in ClinVar as Benign. ClinVar VariationId is 1239931.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145809.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH14	NM_001145809.2	MANE Select	c.4965+278C>G		intron	N/A	NP_001139281.1	Q7Z406-2
	MYH14	NM_001077186.2		c.4866+278C>G		intron	N/A	NP_001070654.1	Q7Z406-6
	MYH14	NM_024729.4		c.4842+278C>G		intron	N/A	NP_079005.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH14	ENST00000642316.2	MANE Select	c.4965+278C>G		intron	N/A	ENSP00000493594.1	Q7Z406-2
	MYH14	ENST00000425460.6	TSL:5	c.4866+278C>G		intron	N/A	ENSP00000407879.1	Q7Z406-6
	MYH14	ENST00000598205.5	TSL:5	c.4866+278C>G		intron	N/A	ENSP00000472543.1	Q7Z406-6

Frequencies

GnomAD3 genomes AF: 0.669 AC: 101441 AN: 151692 Hom.: 35582 Cov.: 29

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.772

Gnomad ASJ AF: 0.769

Gnomad EAS AF: 0.918

Gnomad SAS AF: 0.779

Gnomad FIN AF: 0.761

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.737

Gnomad OTH AF: 0.685

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.669 AC: 101509 AN: 151810 Hom.: 35607 Cov.: 29 AF XY: 0.676 AC XY: 50161 AN XY: 74188

African (AFR) AF: 0.441 AC: 18213 AN: 41338

American (AMR) AF: 0.773 AC: 11798 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.769 AC: 2669 AN: 3470

East Asian (EAS) AF: 0.919 AC: 4720 AN: 5138

South Asian (SAS) AF: 0.779 AC: 3754 AN: 4816

European-Finnish (FIN) AF: 0.761 AC: 8030 AN: 10556

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.737 AC: 50076 AN: 67918

Other (OTH) AF: 0.688 AC: 1449 AN: 2106

Alfa AF: 0.701 Hom.: 4797

Bravo AF: 0.660

Asia WGS AF: 0.833 AC: 2896 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.9
DANN	Benign	0.66
PhyloP100		0.42
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs588035; hg19: chr19-50793183;