19-50210154-C-A

Position:

• chr19-50210154-C-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2839 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH14	NM_001145809.2	c.-3-209C>A		intron_variant		ENST00000642316.2	NP_001139281.1
MYH14	NM_001077186.2	c.-3-209C>A		intron_variant			NP_001070654.1
MYH14	NM_024729.4	c.-3-209C>A		intron_variant			NP_079005.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH14	ENST00000642316.2	c.-3-209C>A		intron_variant			NM_001145809.2	ENSP00000493594

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

Gnomad4 AFR AF: 0.00433

Gnomad4 AMR AF: 0.0158

Gnomad4 ASJ AF: 0.0284

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0398

Gnomad4 FIN AF: 0.0355

Gnomad4 NFE AF: 0.0271

Gnomad4 OTH AF: 0.0261

Alfa AF: 0.0239 Hom.: 10

Bravo AF: 0.0172

Asia WGS AF: 0.0130 AC: 47 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.4
DANN	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs73060990; hg19: chr19-50713411;