chr19-50232083-C-T

Position:

• chr19-50232083-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.914

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]

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH14	NM_001145809.2	c.1114+13C>T		intron_variant		ENST00000642316.2
MYH14	NM_001077186.2	c.1114+13C>T		intron_variant
MYH14	NM_024729.4	c.1090+13C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH14	ENST00000642316.2	c.1114+13C>T		intron_variant			NM_001145809.2

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49705 AN: 152042 Hom.: 8473 Cov.: 33

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

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.: 41 AF XY: 0.367 AC XY: 266297 AN XY: 724958

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.: 33 AF XY: 0.329 AC XY: 24453 AN XY: 74360

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

Submissions by phenotype

not specified Benign:4

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 07, 2012	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). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

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	- -

Autosomal dominant nonsyndromic hearing loss 4A Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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	-0.90
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

Other links and lift over

dbSNP: rs11666328; hg19: chr19-50735340; COSMIC: COSV51812952;