rs76579307

Variant names:

• chr19-50276212-C-T
• rs76579307
• NM_001145809.2:c.3680+9C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001145809.2(MYH14):​c.3680+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 1,525,978 control chromosomes in the GnomAD database, including 39,304 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3347 hom., cov: 33)
  • Exomes 𝑓: 0.22 (35957 hom.)
• Consequence: MYH14 NM_001145809.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -3.50
• Publications: 3 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 19-50276212-C-T is Benign according to our data. Variant chr19-50276212-C-T is described in ClinVar as Benign. ClinVar VariationId is 44067.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.236 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.3680+9C>T		intron	N/A	NP_001139281.1
	MYH14	NM_001077186.2		c.3581+9C>T		intron	N/A	NP_001070654.1
	MYH14	NM_024729.4		c.3557+9C>T		intron	N/A	NP_079005.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH14	ENST00000642316.2	MANE Select	c.3680+9C>T		intron	N/A	ENSP00000493594.1
	MYH14	ENST00000425460.6	TSL:5	c.3581+9C>T		intron	N/A	ENSP00000407879.1
	MYH14	ENST00000598205.5	TSL:5	c.3581+9C>T		intron	N/A	ENSP00000472543.1

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30533 AN: 152090 Hom.: 3347 Cov.: 33

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.0322

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.195

GnomAD2 exomes AF: 0.184 AC: 24583 AN: 133464 AF XY: 0.182

Gnomad AFR exome AF: 0.157

Gnomad AMR exome AF: 0.149

Gnomad ASJ exome AF: 0.161

Gnomad EAS exome AF: 0.0199

Gnomad FIN exome AF: 0.301

Gnomad NFE exome AF: 0.239

Gnomad OTH exome AF: 0.198

GnomAD4 exome AF: 0.222 AC: 305190 AN: 1373770 Hom.: 35957 Cov.: 30 AF XY: 0.219 AC XY: 148194 AN XY: 675730

African (AFR) AF: 0.152 AC: 4710 AN: 31070

American (AMR) AF: 0.146 AC: 4990 AN: 34226

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 3929 AN: 24288

East Asian (EAS) AF: 0.0177 AC: 628 AN: 35474

South Asian (SAS) AF: 0.121 AC: 9366 AN: 77232

European-Finnish (FIN) AF: 0.291 AC: 12944 AN: 44530

Middle Eastern (MID) AF: 0.152 AC: 608 AN: 3992

European-Non Finnish (NFE) AF: 0.241 AC: 256812 AN: 1066124

Other (OTH) AF: 0.197 AC: 11203 AN: 56834

GnomAD4 genome AF: 0.201 AC: 30539 AN: 152208 Hom.: 3347 Cov.: 33 AF XY: 0.201 AC XY: 14966 AN XY: 74420

African (AFR) AF: 0.156 AC: 6483 AN: 41546

American (AMR) AF: 0.165 AC: 2526 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 537 AN: 3472

East Asian (EAS) AF: 0.0323 AC: 167 AN: 5178

South Asian (SAS) AF: 0.115 AC: 553 AN: 4822

European-Finnish (FIN) AF: 0.301 AC: 3185 AN: 10588

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.240 AC: 16283 AN: 67984

Other (OTH) AF: 0.193 AC: 407 AN: 2110

Alfa AF: 0.216 Hom.: 813

Bravo AF: 0.190

Asia WGS AF: 0.0960 AC: 333 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	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	-0.89
CADD	Benign	0.23
DANN	Benign	0.75
PhyloP100		-3.5
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: rs76579307; hg19: chr19-50779469;