19-50223349-C-G
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_001145809.2(MYH14):c.693C>G(p.Pro231Pro) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000256 in 1,563,998 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P231P) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
MYH14
NM_001145809.2 splice_region, synonymous
NM_001145809.2 splice_region, synonymous
Scores
2
Splicing: ADA: 0.00005543
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.533
Publications
3 publications found
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 Gene-Disease associations (from GenCC):
- autosomal dominant nonsyndromic hearing loss 4AInheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
- peripheral neuropathy-myopathy-hoarseness-hearing loss syndromeInheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
- nonsyndromic genetic hearing lossInheritance: AD Classification: MODERATE Submitted by: ClinGen
- autosomal dominant nonsyndromic hearing lossInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP7
Synonymous conserved (PhyloP=-0.533 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| MYH14 | NM_001145809.2 | c.693C>G | p.Pro231Pro | splice_region_variant, synonymous_variant | Exon 5 of 43 | ENST00000642316.2 | NP_001139281.1 | |
| MYH14 | NM_001077186.2 | c.693C>G | p.Pro231Pro | splice_region_variant, synonymous_variant | Exon 5 of 42 | NP_001070654.1 | ||
| MYH14 | NM_024729.4 | c.693C>G | p.Pro231Pro | splice_region_variant, synonymous_variant | Exon 5 of 41 | NP_079005.3 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| MYH14 | ENST00000642316.2 | c.693C>G | p.Pro231Pro | splice_region_variant, synonymous_variant | Exon 5 of 43 | NM_001145809.2 | ENSP00000493594.1 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152238Hom.: 0 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152238
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000213 AC: 3AN: 1411760Hom.: 0 Cov.: 32 AF XY: 0.00000286 AC XY: 2AN XY: 698150 show subpopulations
GnomAD4 exome
AF:
AC:
3
AN:
1411760
Hom.:
Cov.:
32
AF XY:
AC XY:
2
AN XY:
698150
show subpopulations
African (AFR)
AF:
AC:
0
AN:
32112
American (AMR)
AF:
AC:
0
AN:
36962
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25312
East Asian (EAS)
AF:
AC:
0
AN:
36478
South Asian (SAS)
AF:
AC:
0
AN:
80816
European-Finnish (FIN)
AF:
AC:
0
AN:
50146
Middle Eastern (MID)
AF:
AC:
0
AN:
5710
European-Non Finnish (NFE)
AF:
AC:
3
AN:
1085624
Other (OTH)
AF:
AC:
0
AN:
58600
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.542
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
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>80
Age
GnomAD4 genome 0.00000657 AC: 1AN: 152238Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74378 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152238
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
74378
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41464
American (AMR)
AF:
AC:
0
AN:
15286
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5190
South Asian (SAS)
AF:
AC:
0
AN:
4832
European-Finnish (FIN)
AF:
AC:
0
AN:
10632
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
1
AN:
68044
Other (OTH)
AF:
AC:
0
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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