chr19-50210398-G-C

Variant names:

• chr19-50210398-G-C
• rs8106196
• NM_001145809.2:c.33G>C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001145809.2(MYH14):​c.33G>C​(p.Arg11Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0275 in 1,580,478 control chromosomes in the GnomAD database, including 730 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. R11R) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.032 (100 hom., cov: 32)
  • Exomes 𝑓: 0.027 (630 hom.)
• Consequence: MYH14 NM_001145809.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 1.62

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 19-50210398-G-C is Benign according to our data. Variant chr19-50210398-G-C is described in ClinVar as [Benign]. Clinvar id is 44065.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50210398-G-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=1.62 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH14	NM_001145809.2	c.33G>C	p.Arg11Arg	synonymous_variant	Exon 2 of 43	ENST00000642316.2	NP_001139281.1
MYH14	NM_001077186.2	c.33G>C	p.Arg11Arg	synonymous_variant	Exon 2 of 42		NP_001070654.1
MYH14	NM_024729.4	c.33G>C	p.Arg11Arg	synonymous_variant	Exon 2 of 41		NP_079005.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH14	ENST00000642316.2	c.33G>C	p.Arg11Arg	synonymous_variant	Exon 2 of 43		NM_001145809.2	ENSP00000493594.1

Frequencies

GnomAD3 genomes AF: 0.0316 AC: 4806 AN: 152122 Hom.: 99 Cov.: 32

Gnomad AFR AF: 0.0479

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0188

Gnomad ASJ AF: 0.0579

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0165

Gnomad FIN AF: 0.0283

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0271

Gnomad OTH AF: 0.0312

GnomAD3 exomes AF: 0.0241 AC: 4594 AN: 190242 Hom.: 68 AF XY: 0.0245 AC XY: 2585 AN XY: 105366

Gnomad AFR exome AF: 0.0474

Gnomad AMR exome AF: 0.0146

Gnomad ASJ exome AF: 0.0498

Gnomad EAS exome AF: 0.0000704

Gnomad SAS exome AF: 0.0148

Gnomad FIN exome AF: 0.0280

Gnomad NFE exome AF: 0.0286

Gnomad OTH exome AF: 0.0289

GnomAD4 exome AF: 0.0271 AC: 38679 AN: 1428238 Hom.: 630 Cov.: 31 AF XY: 0.0269 AC XY: 19053 AN XY: 708706

Gnomad4 AFR exome AF: 0.0542

Gnomad4 AMR exome AF: 0.0150

Gnomad4 ASJ exome AF: 0.0504

Gnomad4 EAS exome AF: 0.0000806

Gnomad4 SAS exome AF: 0.0153

Gnomad4 FIN exome AF: 0.0291

Gnomad4 NFE exome AF: 0.0277

Gnomad4 OTH exome AF: 0.0291

GnomAD4 genome AF: 0.0316 AC: 4814 AN: 152240 Hom.: 100 Cov.: 32 AF XY: 0.0319 AC XY: 2377 AN XY: 74460

Gnomad4 AFR AF: 0.0480

Gnomad4 AMR AF: 0.0188

Gnomad4 ASJ AF: 0.0579

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0163

Gnomad4 FIN AF: 0.0283

Gnomad4 NFE AF: 0.0271

Gnomad4 OTH AF: 0.0308

Alfa AF: 0.0226 Hom.: 20

Bravo AF: 0.0317

Asia WGS AF: 0.0140 AC: 51 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:6

Apr 30, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Arg11Arg in Exon 02 of MYH14: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 3.9% (94/2438) of Afri can American chromosomes from a broad population by the NHLBI Exome Sequencing P roject (http://evs.gs.washington.edu/EVS; dbSNP rs8106196). -

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PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 05, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 03, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:4

Feb 18, 2019

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 11, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 28, 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

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	12
DANN	Benign	0.69

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: rs8106196; hg19: chr19-50713655;