19-50189839-T-C

Variant names:

• chr19-50189839-T-C
• rs648691
• ENST00000598205.5:c.-4+1532T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000943710.1(MYH14):​c.-4+1532T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 152,052 control chromosomes in the GnomAD database, including 12,019 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.39 (12019 hom., cov: 32)
• Consequence: MYH14 ENST00000943710.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.11
• Publications: 5 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

ENSG00000301778 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000943710.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH14	ENST00000598205.5	TSL:5	c.-4+1532T>C		intron	N/A	ENSP00000472543.1	Q7Z406-6
	MYH14	ENST00000943710.1		c.-4+1532T>C		intron	N/A	ENSP00000613769.1
	ENSG00000301778	ENST00000781781.1		n.142+13974A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59779 AN: 151932 Hom.: 12006 Cov.: 32

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.387

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

GnomAD4 genome AF: 0.393 AC: 59828 AN: 152052 Hom.: 12019 Cov.: 32 AF XY: 0.393 AC XY: 29237 AN XY: 74342

African (AFR) AF: 0.344 AC: 14241 AN: 41458

American (AMR) AF: 0.366 AC: 5582 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1037 AN: 3472

East Asian (EAS) AF: 0.293 AC: 1517 AN: 5178

South Asian (SAS) AF: 0.295 AC: 1423 AN: 4828

European-Finnish (FIN) AF: 0.459 AC: 4853 AN: 10574

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.438 AC: 29754 AN: 67962

Other (OTH) AF: 0.386 AC: 815 AN: 2112

Alfa AF: 0.414 Hom.: 6995

Bravo AF: 0.384

Asia WGS AF: 0.293 AC: 1020 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.50
DANN	Benign	0.52
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs648691; hg19: chr19-50693096;