rs181567755

Positions:

• chr19-50309670-G-A
• chr19-50309670-G-C
• chr19-50309670-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001145809.2(MYH14):​c.5991G>A​(p.Thr1997Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000209 in 1,485,222 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00082 (1 hom., cov: 30)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: MYH14 NM_001145809.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -9.18

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 19-50309670-G-A is Benign according to our data. Variant chr19-50309670-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 164208.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-9.18 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000817 (118/144380) while in subpopulation AFR AF= 0.00284 (111/39108). AF 95% confidence interval is 0.00241. There are 1 homozygotes in gnomad4. There are 57 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 118 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH14	NM_001145809.2	c.5991G>A	p.Thr1997Thr	synonymous_variant	43/43	ENST00000642316.2	NP_001139281.1
MYH14	NM_001077186.2	c.5892G>A	p.Thr1964Thr	synonymous_variant	42/42		NP_001070654.1
MYH14	NM_024729.4	c.5868G>A	p.Thr1956Thr	synonymous_variant	41/41		NP_079005.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH14	ENST00000642316.2	c.5991G>A	p.Thr1997Thr	synonymous_variant	43/43		NM_001145809.2	ENSP00000493594.1

Frequencies

GnomAD3 genomes AF: 0.000804 AC: 116 AN: 144276 Hom.: 1 Cov.: 30

Gnomad AFR AF: 0.00279

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000281

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000451

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000265 AC: 64 AN: 241476 Hom.: 0 AF XY: 0.000251 AC XY: 33 AN XY: 131216

Gnomad AFR exome AF: 0.00328

Gnomad AMR exome AF: 0.0000883

Gnomad ASJ exome AF: 0.000303

Gnomad EAS exome AF: 0.000114

Gnomad SAS exome AF: 0.0000678

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000459

Gnomad OTH exome AF: 0.000170

GnomAD4 exome AF: 0.000144 AC: 193 AN: 1340842 Hom.: 0 Cov.: 35 AF XY: 0.000129 AC XY: 86 AN XY: 664868

Gnomad4 AFR exome AF: 0.00350

Gnomad4 AMR exome AF: 0.0000739

Gnomad4 ASJ exome AF: 0.000138

Gnomad4 EAS exome AF: 0.000261

Gnomad4 SAS exome AF: 0.0000475

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000570

Gnomad4 OTH exome AF: 0.000191

GnomAD4 genome AF: 0.000817 AC: 118 AN: 144380 Hom.: 1 Cov.: 30 AF XY: 0.000813 AC XY: 57 AN XY: 70120

Gnomad4 AFR AF: 0.00284

Gnomad4 AMR AF: 0.000280

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000451

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000229 Hom.: 0

Bravo AF: 0.000812

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 19, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 08, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Oct 25, 2016

p.Thr1997Thr in exon 43 of MYH14: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence, and has been identified in 0.5% (34/6448) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broad institute.org; dbSNP rs181567755). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.045
DANN	Benign	0.94

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs181567755; hg19: chr19-50812927;