chr19-50260632-C-T

Position:

chr19-50260632-C-T

Variant summary

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

The NM_001145809.2(MYH14):c.2355-14C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 1,600,692 control chromosomes in the GnomAD database, including 157,937 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16467 hom., cov: 28)

Exomes 𝑓: 0.44 ( 141470 hom. )

Consequence

MYH14
NM_001145809.2 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.110

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 19-50260632-C-T is Benign according to our data. Variant chr19-50260632-C-T is described in ClinVar as [Benign]. Clinvar id is 44057.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50260632-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
MYH14	NM_001145809.2 linkuse as main transcript	c.2355-14C>T	splice_polypyrimidine_tract_variant, intron_variant	ENST00000642316.2	NP_001139281.1
MYH14	NM_001077186.2 linkuse as main transcript	c.2256-14C>T	splice_polypyrimidine_tract_variant, intron_variant		NP_001070654.1
MYH14	NM_024729.4 linkuse as main transcript	c.2232-14C>T	splice_polypyrimidine_tract_variant, intron_variant		NP_079005.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH14	ENST00000642316.2 linkuse as main transcript	c.2355-14C>T		splice_polypyrimidine_tract_variant, intron_variant			NM_001145809.2	ENSP00000493594		Q7Z406-2

Frequencies

GnomAD3 genomes

AF:

0.459

AC:

69507

AN:

151346

Hom.:

16445

Cov.:

show subpopulations

Gnomad AFR

AF:

0.467

Gnomad AMI

AF:

0.560

Gnomad AMR

AF:

0.592

Gnomad ASJ

AF:

0.294

Gnomad EAS

AF:

0.310

Gnomad SAS

AF:

0.392

Gnomad FIN

AF:

0.536

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.437

Gnomad OTH

AF:

0.440

GnomAD3 exomes

AF:

0.454

AC:

111813

AN:

246398

Hom.:

26624

AF XY:

0.442

AC XY:

59172

AN XY:

133854

show subpopulations

Gnomad AFR exome

AF:

0.468

Gnomad AMR exome

AF:

0.662

Gnomad ASJ exome

AF:

0.283

Gnomad EAS exome

AF:

0.302

Gnomad SAS exome

AF:

0.385

Gnomad FIN exome

AF:

0.526

Gnomad NFE exome

AF:

0.433

Gnomad OTH exome

AF:

0.443

GnomAD4 exome

AF:

0.437

AC:

633783

AN:

1449228

Hom.:

141470

Cov.:

AF XY:

0.434

AC XY:

313544

AN XY:

721636

show subpopulations

Gnomad4 AFR exome

AF:

0.467

Gnomad4 AMR exome

AF:

0.649

Gnomad4 ASJ exome

AF:

0.292

Gnomad4 EAS exome

AF:

0.322

Gnomad4 SAS exome

AF:

0.388

Gnomad4 FIN exome

AF:

0.520

Gnomad4 NFE exome

AF:

0.436

Gnomad4 OTH exome

AF:

0.426

GnomAD4 genome

AF:

0.459

AC:

69577

AN:

151464

Hom.:

16467

Cov.:

AF XY:

0.465

AC XY:

34387

AN XY:

73974

show subpopulations

Gnomad4 AFR

AF:

0.467

Gnomad4 AMR

AF:

0.592

Gnomad4 ASJ

AF:

0.294

Gnomad4 EAS

AF:

0.311

Gnomad4 SAS

AF:

0.393

Gnomad4 FIN

AF:

0.536

Gnomad4 NFE

AF:

0.437

Gnomad4 OTH

AF:

0.435

Alfa

AF:

0.426

Hom.:

2623

Bravo

AF:

0.465

Asia WGS

AF:

0.403

AC:

1398

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 22, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 07, 2012	2355-14C>T in Intron 19 of MYH14: This variant is not expected to have clinical significance because it has been identified in 45.9% (1652/3600) of African Amer ican chromosomes from a broad population by the NHLBI Exome Sequencing Project ( http://evs.gs.washington.edu/EVS; dbSNP rs12981413). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Autosomal dominant nonsyndromic hearing loss 4A

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -

Peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

5.6

DANN

Benign

0.64

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