19-50210400-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001145809.2(MYH14):ā€‹c.35A>Gā€‹(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 (ā˜…). Synonymous variant affecting the same amino acid position (i.e. K12K) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

MYH14
NM_001145809.2 missense

Scores

2
4
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.82
Variant links:
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]

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ACMG classification

Classification made for transcript

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
MYH14NM_001145809.2 linkc.35A>G p.Lys12Arg missense_variant Exon 2 of 43 ENST00000642316.2 NP_001139281.1 Q7Z406-2A1L2Z2B3KWH4
MYH14NM_001077186.2 linkc.35A>G p.Lys12Arg missense_variant Exon 2 of 42 NP_001070654.1 Q7Z406-6B3KWH4
MYH14NM_024729.4 linkc.35A>G p.Lys12Arg missense_variant Exon 2 of 41 NP_079005.3 Q7Z406-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MYH14ENST00000642316.2 linkc.35A>G p.Lys12Arg missense_variant Exon 2 of 43 NM_001145809.2 ENSP00000493594.1 Q7Z406-2

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
LINK: link

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; API