NM_001145809.2:c.1149T>C

Variant names:

• chr19-50244276-T-C
• rs61734424
• NM_001145809.2:c.1149T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001145809.2(MYH14):​c.1149T>C​(p.Phe383Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.043 in 1,613,776 control chromosomes in the GnomAD database, including 2,561 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.060 (415 hom., cov: 31)
  • Exomes 𝑓: 0.041 (2146 hom.)
• Consequence: MYH14 NM_001145809.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.57
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss 4A

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 19-50244276-T-C is Benign according to our data. Variant chr19-50244276-T-C is described in ClinVar as Benign. ClinVar VariationId is 44046.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.57 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145809.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH14	NM_001145809.2	MANE Select	c.1149T>C	p.Phe383Phe	synonymous	Exon 11 of 43	NP_001139281.1	Q7Z406-2
	MYH14	NM_001077186.2		c.1149T>C	p.Phe383Phe	synonymous	Exon 11 of 42	NP_001070654.1	Q7Z406-6
	MYH14	NM_024729.4		c.1125T>C	p.Phe375Phe	synonymous	Exon 10 of 41	NP_079005.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH14	ENST00000642316.2	MANE Select	c.1149T>C	p.Phe383Phe	synonymous	Exon 11 of 43	ENSP00000493594.1	Q7Z406-2
	MYH14	ENST00000599920.5	TSL:1	c.1149T>C	p.Phe383Phe	synonymous	Exon 11 of 24	ENSP00000469573.1	M0QY43
	MYH14	ENST00000425460.6	TSL:5	c.1149T>C	p.Phe383Phe	synonymous	Exon 11 of 42	ENSP00000407879.1	Q7Z406-6

Frequencies

GnomAD3 genomes AF: 0.0600 AC: 9124 AN: 152062 Hom.: 409 Cov.: 31

Gnomad AFR AF: 0.0871

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.0455

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.0317

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0328

Gnomad OTH AF: 0.0621

GnomAD2 exomes AF: 0.0653 AC: 16232 AN: 248718 AF XY: 0.0581

Gnomad AFR exome AF: 0.0873

Gnomad AMR exome AF: 0.200

Gnomad ASJ exome AF: 0.0515

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.107

Gnomad NFE exome AF: 0.0333

Gnomad OTH exome AF: 0.0572

GnomAD4 exome AF: 0.0412 AC: 60244 AN: 1461596 Hom.: 2146 Cov.: 32 AF XY: 0.0402 AC XY: 29256 AN XY: 727096

African (AFR) AF: 0.0833 AC: 2788 AN: 33476

American (AMR) AF: 0.191 AC: 8529 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0520 AC: 1358 AN: 26132

East Asian (EAS) AF: 0.00207 AC: 82 AN: 39696

South Asian (SAS) AF: 0.0362 AC: 3126 AN: 86258

European-Finnish (FIN) AF: 0.106 AC: 5672 AN: 53358

Middle Eastern (MID) AF: 0.0307 AC: 177 AN: 5768

European-Non Finnish (NFE) AF: 0.0322 AC: 35795 AN: 1111820

Other (OTH) AF: 0.0450 AC: 2717 AN: 60368

GnomAD4 genome AF: 0.0602 AC: 9154 AN: 152180 Hom.: 415 Cov.: 31 AF XY: 0.0629 AC XY: 4676 AN XY: 74398

African (AFR) AF: 0.0873 AC: 3625 AN: 41528

American (AMR) AF: 0.113 AC: 1723 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0455 AC: 158 AN: 3472

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5168

South Asian (SAS) AF: 0.0315 AC: 152 AN: 4826

European-Finnish (FIN) AF: 0.104 AC: 1106 AN: 10588

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0328 AC: 2232 AN: 68006

Other (OTH) AF: 0.0615 AC: 130 AN: 2114

Alfa AF: 0.0436 Hom.: 148

Bravo AF: 0.0655

Asia WGS AF: 0.0330 AC: 113 AN: 3478

EpiCase AF: 0.0338

EpiControl AF: 0.0307

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	1	Autosomal dominant nonsyndromic hearing loss 4A (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.70
DANN	Benign	0.41
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs61734424; hg19: chr19-50747533; COSMIC: COSV51835389;