NM_001145809.2:c.693+12C>T

Variant names:

• chr19-50223361-C-T
• rs370673291
• NM_001145809.2:c.693+12C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001145809.2(MYH14):​c.693+12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000116 in 1,544,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: MYH14 NM_001145809.2 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.694

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 19-50223361-C-T is Benign according to our data. Variant chr19-50223361-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 164166.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50223361-C-T is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000138 (21/152384) while in subpopulation SAS AF= 0.000828 (4/4832). AF 95% confidence interval is 0.000282. There are 0 homozygotes in gnomad4. There are 8 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 21 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH14	NM_001145809.2	c.693+12C>T		intron_variant	Intron 5 of 42	ENST00000642316.2	NP_001139281.1
MYH14	NM_001077186.2	c.693+12C>T		intron_variant	Intron 5 of 41		NP_001070654.1
MYH14	NM_024729.4	c.693+12C>T		intron_variant	Intron 5 of 40		NP_079005.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH14	ENST00000642316.2	c.693+12C>T		intron_variant	Intron 5 of 42		NM_001145809.2	ENSP00000493594.1

Frequencies

GnomAD3 genomes AF: 0.000138 AC: 21 AN: 152266 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000211 AC: 35 AN: 166106 Hom.: 0 AF XY: 0.000306 AC XY: 27 AN XY: 88232

Gnomad AFR exome AF: 0.000114

Gnomad AMR exome AF: 0.000159

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000640

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000224

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000114 AC: 158 AN: 1391890 Hom.: 0 Cov.: 27 AF XY: 0.000126 AC XY: 87 AN XY: 688358

Gnomad4 AFR exome AF: 0.0000316

Gnomad4 AMR exome AF: 0.000138

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000790

Gnomad4 FIN exome AF: 0.0000604

Gnomad4 NFE exome AF: 0.0000598

Gnomad4 OTH exome AF: 0.000259

GnomAD4 genome AF: 0.000138 AC: 21 AN: 152384 Hom.: 0 Cov.: 33 AF XY: 0.000107 AC XY: 8 AN XY: 74526

Gnomad4 AFR AF: 0.0000240

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000828

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000304 Hom.: 0

Bravo AF: 0.000113

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Aug 19, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

Apr 30, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

c.693+12C>T in intron 5 of MYH14: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus seq uence and has been identified in 1/3468 African American chromosomes by the NHLB I Exome Sequencing Project (http://evs.gs.washington.edu/EVS). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.96
DANN	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs370673291; hg19: chr19-50726618;