rs115019972

chr19-50280348-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001145809.2(MYH14):c.4255C>T(p.Arg1419Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000942 in 1,547,494 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0051 (6 hom., cov: 32)
  • Exomes 𝑓: 0.00049 (7 hom.)
• Consequence: MYH14 NM_001145809.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 4.36

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 (MetaRNN=0.0073207915).
• BP6: Variant 19-50280348-C-T is Benign according to our data. Variant chr19-50280348-C-T is described in ClinVar as [Benign]. Clinvar id is 164189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50280348-C-T is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00507 (772/152270) while in subpopulation AFR AF= 0.0175 (727/41550). AF 95% confidence interval is 0.0164. There are 6 homozygotes in gnomad4. There are 364 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 773 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH14	NM_001145809.2	c.4255C>T	p.Arg1419Trp	missense_variant	32/43	ENST00000642316.2
MYH14	NM_001077186.2	c.4156C>T	p.Arg1386Trp	missense_variant	31/42
MYH14	NM_024729.4	c.4132C>T	p.Arg1378Trp	missense_variant	30/41

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH14	ENST00000642316.2	c.4255C>T	p.Arg1419Trp	missense_variant	32/43		NM_001145809.2

Frequencies

GnomAD3 genomes AF: 0.00508 AC: 773 AN: 152152 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0176

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.000986 AC: 150 AN: 152134 Hom.: 0 AF XY: 0.000693 AC XY: 56 AN XY: 80752

Gnomad AFR exome AF: 0.0152

Gnomad AMR exome AF: 0.00110

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000923

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000701

GnomAD4 exome AF: 0.000491 AC: 685 AN: 1395224 Hom.: 7 Cov.: 32 AF XY: 0.000394 AC XY: 271 AN XY: 687778

Gnomad4 AFR exome AF: 0.0175

Gnomad4 AMR exome AF: 0.00110

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000507

Gnomad4 FIN exome AF: 0.0000204

Gnomad4 NFE exome AF: 0.0000204

Gnomad4 OTH exome AF: 0.00114

GnomAD4 genome AF: 0.00507 AC: 772 AN: 152270 Hom.: 6 Cov.: 32 AF XY: 0.00489 AC XY: 364 AN XY: 74444

Gnomad4 AFR AF: 0.0175

Gnomad4 AMR AF: 0.00242

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00227 Hom.: 1

Bravo AF: 0.00545

ESP6500AA AF: 0.0118 AC: 38

ESP6500EA AF: 0.000157 AC: 1

ExAC AF: 0.00116 AC: 35

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Feb 27, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 18, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 18, 2019	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

May 07, 2012

Arg1419Trp in Exon 32 of MYH14: This variant is not expected to have clinical si gnificance because it has been identified in 1.0% (26/2612) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs115019972). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.25
Cadd	Pathogenic	32
Dann	Uncertain	1.0
Eigen	Benign	-0.042
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.82	D
MetaRNN	Benign	0.0073	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.72	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Uncertain	0.77	T
Sift4G	Uncertain	0.0060	D;D;D;D;.;D;D;D
Polyphen		1.0	D;.;D;D;D;D;D;.
Vest4		0.17
MVP		0.50
MPC		0.64
ClinPred		0.039	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.31

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: rs115019972; hg19: chr19-50783605; COSMIC: COSV51826375; COSMIC: COSV51826375;