NM_001145809.2:c.5469+16C>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.5469+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 1,542,138 control chromosomes in the GnomAD database, including 424,673 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 35484 hom., cov: 33)

Exomes 𝑓: 0.74 ( 389189 hom. )

Consequence

MYH14
NM_001145809.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -4.41

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=-0.86).

BP6

Variant 19-50293703-C-T is Benign according to our data. Variant chr19-50293703-C-T is described in ClinVar as [Benign]. Clinvar id is 257578.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50293703-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MYH14	NM_001145809.2 link	c.5469+16C>T	intron_variant	Intron 39 of 42	ENST00000642316.2	NP_001139281.1	Q7Z406-2A1L2Z2B3KWH4
MYH14	NM_001077186.2 link	c.5370+16C>T	intron_variant	Intron 38 of 41		NP_001070654.1	Q7Z406-6B3KWH4
MYH14	NM_024729.4 link	c.5346+16C>T	intron_variant	Intron 37 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.5469+16C>T		intron_variant	Intron 39 of 42		NM_001145809.2	ENSP00000493594.1		Q7Z406-2

Frequencies

GnomAD3 genomes

AF:

0.661

AC:

100501

AN:

152014

Hom.:

35464

Cov.:

show subpopulations

Gnomad AFR

AF:

0.394

Gnomad AMI

AF:

0.646

Gnomad AMR

AF:

0.773

Gnomad ASJ

AF:

0.722

Gnomad EAS

AF:

0.922

Gnomad SAS

AF:

0.779

Gnomad FIN

AF:

0.764

Gnomad MID

AF:

0.722

Gnomad NFE

AF:

0.750

Gnomad OTH

AF:

0.685

GnomAD3 exomes

AF:

0.754

AC:

149415

AN:

198216

Hom.:

57800

AF XY:

0.757

AC XY:

79877

AN XY:

105494

show subpopulations

Gnomad AFR exome

AF:

0.388

Gnomad AMR exome

AF:

0.857

Gnomad ASJ exome

AF:

0.711

Gnomad EAS exome

AF:

0.931

Gnomad SAS exome

AF:

0.781

Gnomad FIN exome

AF:

0.768

Gnomad NFE exome

AF:

0.747

Gnomad OTH exome

AF:

0.747

GnomAD4 exome

AF:

0.745

AC:

1035465

AN:

1390006

Hom.:

389189

Cov.:

AF XY:

0.746

AC XY:

509743

AN XY:

683016

show subpopulations

Gnomad4 AFR exome

AF:

0.384

Gnomad4 AMR exome

AF:

0.846

Gnomad4 ASJ exome

AF:

0.713

Gnomad4 EAS exome

AF:

0.910

Gnomad4 SAS exome

AF:

0.785

Gnomad4 FIN exome

AF:

0.766

Gnomad4 NFE exome

AF:

0.744

Gnomad4 OTH exome

AF:

0.725

GnomAD4 genome

AF:

0.661

AC:

100560

AN:

152132

Hom.:

35484

Cov.:

AF XY:

0.669

AC XY:

49765

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.394

Gnomad4 AMR

AF:

0.774

Gnomad4 ASJ

AF:

0.722

Gnomad4 EAS

AF:

0.923

Gnomad4 SAS

AF:

0.779

Gnomad4 FIN

AF:

0.764

Gnomad4 NFE

AF:

0.750

Gnomad4 OTH

AF:

0.688

Alfa

AF:

0.722

Hom.:

13602

Bravo

AF:

0.651

Asia WGS

AF:

0.838

AC:

2912

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 22, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal dominant nonsyndromic hearing loss 4A

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

-0.86

CADD

Benign

0.034

DANN

Benign

0.52

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