19-50232083-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001145809.2(MYH14):c.1114+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 1,609,156 control chromosomes in the GnomAD database, including 107,029 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 8472 hom., cov: 33)

Exomes 𝑓: 0.37 ( 98557 hom. )

Consequence

MYH14
NM_001145809.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.914

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 19-50232083-C-T is Benign according to our data. Variant chr19-50232083-C-T is described in ClinVar as [Benign]. Clinvar id is 44044.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50232083-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MYH14	NM_001145809.2 link	c.1114+13C>T	intron_variant	Intron 10 of 42	ENST00000642316.2	NP_001139281.1	Q7Z406-2A1L2Z2B3KWH4
MYH14	NM_001077186.2 link	c.1114+13C>T	intron_variant	Intron 10 of 41		NP_001070654.1	Q7Z406-6B3KWH4
MYH14	NM_024729.4 link	c.1090+13C>T	intron_variant	Intron 9 of 40		NP_079005.3	Q7Z406-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH14	ENST00000642316.2 link	c.1114+13C>T		intron_variant	Intron 10 of 42		NM_001145809.2	ENSP00000493594.1		Q7Z406-2

Frequencies

GnomAD3 genomes

AF:

0.327

AC:

49705

AN:

152042

Hom.:

8473

Cov.:

show subpopulations

Gnomad AFR

AF:

0.232

Gnomad AMI

AF:

0.320

Gnomad AMR

AF:

0.361

Gnomad ASJ

AF:

0.372

Gnomad EAS

AF:

0.366

Gnomad SAS

AF:

0.396

Gnomad FIN

AF:

0.330

Gnomad MID

AF:

0.348

Gnomad NFE

AF:

0.366

Gnomad OTH

AF:

0.335

GnomAD3 exomes

AF:

0.359

AC:

87500

AN:

244048

Hom.:

15976

AF XY:

0.363

AC XY:

48335

AN XY:

132994

show subpopulations

Gnomad AFR exome

AF:

0.225

Gnomad AMR exome

AF:

0.346

Gnomad ASJ exome

AF:

0.376

Gnomad EAS exome

AF:

0.370

Gnomad SAS exome

AF:

0.406

Gnomad FIN exome

AF:

0.325

Gnomad NFE exome

AF:

0.369

Gnomad OTH exome

AF:

0.367

GnomAD4 exome

AF:

0.366

AC:

533198

AN:

1456998

Hom.:

98557

Cov.:

AF XY:

0.367

AC XY:

266297

AN XY:

724958

show subpopulations

Gnomad4 AFR exome

AF:

0.225

Gnomad4 AMR exome

AF:

0.344

Gnomad4 ASJ exome

AF:

0.373

Gnomad4 EAS exome

AF:

0.353

Gnomad4 SAS exome

AF:

0.406

Gnomad4 FIN exome

AF:

0.324

Gnomad4 NFE exome

AF:

0.370

Gnomad4 OTH exome

AF:

0.362

GnomAD4 genome

AF:

0.327

AC:

49718

AN:

152158

Hom.:

8472

Cov.:

AF XY:

0.329

AC XY:

24453

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.232

Gnomad4 AMR

AF:

0.361

Gnomad4 ASJ

AF:

0.372

Gnomad4 EAS

AF:

0.366

Gnomad4 SAS

AF:

0.397

Gnomad4 FIN

AF:

0.330

Gnomad4 NFE

AF:

0.366

Gnomad4 OTH

AF:

0.336

Alfa

AF:

0.304

Hom.:

2022

Bravo

AF:

0.324

Asia WGS

AF:

0.361

AC:

1253

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

1114+13C>T in Intron 10 of MYH14: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus seq uence and has been identified in 36.6% (2438/6660) of European American chromoso mes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs .washington.edu/EVS; dbSNP rs11666328). -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 22, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal dominant nonsyndromic hearing loss 4A

Benign:2

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.027

DANN

Benign

0.71

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over