NM_001145809.2:c.-3-209C>A

Variant names:

• chr19-50210154-C-A
• rs73060990
• NM_001145809.2:c.-3-209C>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001145809.2(MYH14):​c.-3-209C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0197 in 144,084 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.020 (42 hom., cov: 31)
• Consequence: MYH14 NM_001145809.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0480
• Publications: 0 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 19-50210154-C-A is Benign according to our data. Variant chr19-50210154-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1215730.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0197 (2839/144084) while in subpopulation SAS AF = 0.0398 (180/4526). AF 95% confidence interval is 0.035. There are 42 homozygotes in GnomAd4. There are 1393 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2839 AD gene.

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.-3-209C>A		intron	N/A	NP_001139281.1	Q7Z406-2
	MYH14	NM_001077186.2		c.-3-209C>A		intron	N/A	NP_001070654.1	Q7Z406-6
	MYH14	NM_024729.4		c.-3-209C>A		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.-3-209C>A		intron	N/A	ENSP00000493594.1	Q7Z406-2
	MYH14	ENST00000599920.5	TSL:1	c.-3-209C>A		intron	N/A	ENSP00000469573.1	M0QY43
	MYH14	ENST00000425460.6	TSL:5	c.-3-209C>A		intron	N/A	ENSP00000407879.1	Q7Z406-6

Frequencies

GnomAD3 genomes AF: 0.0197 AC: 2839 AN: 144074 Hom.: 42 Cov.: 31

Gnomad AFR AF: 0.00433

Gnomad AMI AF: 0.00566

Gnomad AMR AF: 0.0159

Gnomad ASJ AF: 0.0284

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0391

Gnomad FIN AF: 0.0355

Gnomad MID AF: 0.0448

Gnomad NFE AF: 0.0272

Gnomad OTH AF: 0.0263

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0197 AC: 2839 AN: 144084 Hom.: 42 Cov.: 31 AF XY: 0.0200 AC XY: 1393 AN XY: 69522

African (AFR) AF: 0.00433 AC: 169 AN: 39060

American (AMR) AF: 0.0158 AC: 227 AN: 14340

Ashkenazi Jewish (ASJ) AF: 0.0284 AC: 97 AN: 3418

East Asian (EAS) AF: 0.00 AC: 0 AN: 4910

South Asian (SAS) AF: 0.0398 AC: 180 AN: 4526

European-Finnish (FIN) AF: 0.0355 AC: 291 AN: 8188

Middle Eastern (MID) AF: 0.0492 AC: 13 AN: 264

European-Non Finnish (NFE) AF: 0.0271 AC: 1805 AN: 66504

Other (OTH) AF: 0.0261 AC: 52 AN: 1990

Alfa AF: 0.0222 Hom.: 61

Bravo AF: 0.0172

Asia WGS AF: 0.0130 AC: 47 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.4
DANN	Benign	0.73
PhyloP100		-0.048
PromoterAI		-0.030	Neutral
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: rs73060990; hg19: chr19-50713411;