chr15-57674974-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001018100.5(MYZAP):c.1210G>A(p.Glu404Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,459,094 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 Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
MYZAP
NM_001018100.5 missense
NM_001018100.5 missense
Scores
1
10
6
Clinical Significance
Conservation
PhyloP100: 6.73
Genes affected
MYZAP (HGNC:43444): (myocardial zonula adherens protein) This gene encodes a protein that is abundantly expressed in cardiac tissue. The encoded protein localizes to intercalated discs in cardiomyocytes and functions as an activator of Rho-dependent serum-response factor signaling. Alternative splicing results in multiple transcript variants. Readthrough transcription also exists between this gene and the neighboring downstream gene POLR2M (polymerase (RNA) II (DNA directed) polypeptide M) and is represented with GeneID: 145781. [provided by RefSeq, Mar 2014]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.39106202).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYZAP | NM_001018100.5 | c.1210G>A | p.Glu404Lys | missense_variant | 12/13 | ENST00000267853.10 | |
GCOM1 | NR_104367.2 | n.1868-9428G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYZAP | ENST00000267853.10 | c.1210G>A | p.Glu404Lys | missense_variant | 12/13 | 1 | NM_001018100.5 | P1 | |
MYZAP | ENST00000380565.8 | c.1126G>A | p.Glu376Lys | missense_variant | 11/12 | 1 | |||
MYZAP | ENST00000461709.1 | c.349-9428G>A | intron_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1459094Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 725686
GnomAD4 exome
AF:
AC:
4
AN:
1459094
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
725686
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
Alfa
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Bravo
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 13, 2023 | The c.1210G>A (p.E404K) alteration is located in exon 12 (coding exon 12) of the GCOM1 gene. This alteration results from a G to A substitution at nucleotide position 1210, causing the glutamic acid (E) at amino acid position 404 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;D;D;N
REVEL
Benign
Sift
Uncertain
D;.;D;D;T
Sift4G
Benign
T;T;T;T;D
Polyphen
1.0, 1.0
.;.;.;D;D
Vest4
MutPred
Gain of ubiquitination at E404 (P = 0.0104);Gain of ubiquitination at E404 (P = 0.0104);Gain of ubiquitination at E404 (P = 0.0104);Gain of ubiquitination at E404 (P = 0.0104);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at