19-50232083-C-T

Variant names:

• chr19-50232083-C-T
• rs11666328
• NM_001145809.2:c.1114+13C>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.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
• Publications: 10 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=-0.9).
• BP6: Variant 19-50232083-C-T is Benign according to our data. Variant chr19-50232083-C-T is described in ClinVar as Benign. ClinVar VariationId is 44044.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.382 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.1114+13C>T		intron	N/A	NP_001139281.1
	MYH14	NM_001077186.2		c.1114+13C>T		intron	N/A	NP_001070654.1
	MYH14	NM_024729.4		c.1090+13C>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.1114+13C>T		intron	N/A	ENSP00000493594.1
	MYH14	ENST00000599920.5	TSL:1	c.1114+13C>T		intron	N/A	ENSP00000469573.1
	MYH14	ENST00000425460.6	TSL:5	c.1114+13C>T		intron	N/A	ENSP00000407879.1

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

GnomAD2 exomes AF: 0.359 AC: 87500 AN: 244048 AF XY: 0.363

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 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

African (AFR) AF: 0.225 AC: 7517 AN: 33478

American (AMR) AF: 0.344 AC: 15387 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 9739 AN: 26128

East Asian (EAS) AF: 0.353 AC: 13994 AN: 39692

South Asian (SAS) AF: 0.406 AC: 34973 AN: 86242

European-Finnish (FIN) AF: 0.324 AC: 15904 AN: 49100

Middle Eastern (MID) AF: 0.392 AC: 2262 AN: 5768

European-Non Finnish (NFE) AF: 0.370 AC: 411604 AN: 1111556

Other (OTH) AF: 0.362 AC: 21818 AN: 60330

GnomAD4 genome AF: 0.327 AC: 49718 AN: 152158 Hom.: 8472 Cov.: 33 AF XY: 0.329 AC XY: 24453 AN XY: 74360

African (AFR) AF: 0.232 AC: 9627 AN: 41532

American (AMR) AF: 0.361 AC: 5521 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1287 AN: 3464

East Asian (EAS) AF: 0.366 AC: 1886 AN: 5156

South Asian (SAS) AF: 0.397 AC: 1914 AN: 4820

European-Finnish (FIN) AF: 0.330 AC: 3490 AN: 10580

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.366 AC: 24887 AN: 68000

Other (OTH) AF: 0.336 AC: 710 AN: 2112

Alfa AF: 0.342 Hom.: 15778

Bravo AF: 0.324

Asia WGS AF: 0.361 AC: 1253 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.027
DANN	Benign	0.71
PhyloP100		-0.91
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: rs11666328; hg19: chr19-50735340; COSMIC: COSV51812952;