19-50210092-G-A

Variant names:

• chr19-50210092-G-A
• rs189335033
• NM_001145809.2:c.-3-271G>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.-3-271G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.028 (33 hom., cov: 17)
• Consequence: MYH14 NM_001145809.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0340
• 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: 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 19-50210092-G-A is Benign according to our data. Variant chr19-50210092-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1214402.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0284 (2200/77594) while in subpopulation AMR AF = 0.0343 (149/4348). AF 95% confidence interval is 0.0322. There are 33 homozygotes in GnomAd4. There are 1043 alleles in the male GnomAd4 subpopulation. Median coverage is 17. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2200 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH14	NM_001145809.2	c.-3-271G>A		intron_variant	Intron 1 of 42	ENST00000642316.2	NP_001139281.1
MYH14	NM_001077186.2	c.-3-271G>A		intron_variant	Intron 1 of 41		NP_001070654.1
MYH14	NM_024729.4	c.-3-271G>A		intron_variant	Intron 1 of 40		NP_079005.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH14	ENST00000642316.2	c.-3-271G>A		intron_variant	Intron 1 of 42		NM_001145809.2	ENSP00000493594.1

Frequencies

GnomAD3 genomes AF: 0.0284 AC: 2202 AN: 77564 Hom.: 33 Cov.: 17

Gnomad AFR AF: 0.00799

Gnomad AMI AF: 0.0332

Gnomad AMR AF: 0.0343

Gnomad ASJ AF: 0.0546

Gnomad EAS AF: 0.000913

Gnomad SAS AF: 0.0270

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.0758

Gnomad NFE AF: 0.0336

Gnomad OTH AF: 0.0278

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

GnomAD4 genome AF: 0.0284 AC: 2200 AN: 77594 Hom.: 33 Cov.: 17 AF XY: 0.0311 AC XY: 1043 AN XY: 33582

African (AFR) AF: 0.00798 AC: 142 AN: 17788

American (AMR) AF: 0.0343 AC: 149 AN: 4348

Ashkenazi Jewish (ASJ) AF: 0.0546 AC: 144 AN: 2636

East Asian (EAS) AF: 0.000913 AC: 2 AN: 2190

South Asian (SAS) AF: 0.0264 AC: 46 AN: 1740

European-Finnish (FIN) AF: 0.131 AC: 105 AN: 802

Middle Eastern (MID) AF: 0.0781 AC: 5 AN: 64

European-Non Finnish (NFE) AF: 0.0336 AC: 1562 AN: 46520

Other (OTH) AF: 0.0277 AC: 25 AN: 904

Alfa AF: 0.0226 Hom.: 5

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 08, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.1
DANN	Benign	0.36
PhyloP100		-0.034
PromoterAI		0.021	Neutral
Mutation Taster		=100/0	polymorphism

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: rs189335033; hg19: chr19-50713349;