19-50210400-A-G

Variant names:

• chr19-50210400-A-G
• NM_001145809.2:c.35A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001145809.2(MYH14):​c.35A>G​(p.Lys12Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. K12K) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MYH14 NM_001145809.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.82

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24985772).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH14	NM_001145809.2	c.35A>G	p.Lys12Arg	missense_variant	Exon 2 of 43	ENST00000642316.2	NP_001139281.1
MYH14	NM_001077186.2	c.35A>G	p.Lys12Arg	missense_variant	Exon 2 of 42		NP_001070654.1
MYH14	NM_024729.4	c.35A>G	p.Lys12Arg	missense_variant	Exon 2 of 41		NP_079005.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH14	ENST00000642316.2	c.35A>G	p.Lys12Arg	missense_variant	Exon 2 of 43		NM_001145809.2	ENSP00000493594.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1427034 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 708026

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 30, 2024

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: MYH14 c.35A>G (p.Lys12Arg) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 187364 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.35A>G in individuals affected with MYH14-related conditions and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.079	.;.;T;.;T;.;.;T
Eigen	Benign	-0.097
Eigen_PC	Benign	0.029
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.82	.;T;T;.;T;T;T;.
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.25	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.36	T
MutationAssessor	Benign	1.0	L;L;L;L;.;L;.;L
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.28	.;N;N;.;.;.;.;.
REVEL	Uncertain	0.30
Sift	Benign	0.10	.;T;T;.;.;.;.;.
Sift4G	Pathogenic	0.0	D;D;D;.;T;D;.;D
Polyphen		0.43	B;B;B;B;.;B;.;B
Vest4		0.32
MutPred		0.17		Loss of ubiquitination at K12 (P = 0.0118);Loss of ubiquitination at K12 (P = 0.0118);Loss of ubiquitination at K12 (P = 0.0118);Loss of ubiquitination at K12 (P = 0.0118);Loss of ubiquitination at K12 (P = 0.0118);Loss of ubiquitination at K12 (P = 0.0118);Loss of ubiquitination at K12 (P = 0.0118);Loss of ubiquitination at K12 (P = 0.0118);
MVP		0.62
MPC		0.38
ClinPred		0.57	D
GERP RS		4.3
Varity_R		0.060
gMVP		0.47

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-50713657;