19-53874311-A-C
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_138373.5(MYADM):āc.782A>Cā(p.Tyr261Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,459,432 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000021 ( 0 hom. )
Consequence
MYADM
NM_138373.5 missense
NM_138373.5 missense
Scores
3
10
6
Clinical Significance
Conservation
PhyloP100: 2.83
Genes affected
MYADM (HGNC:7544): (myeloid associated differentiation marker) Involved in several processes, including negative regulation of heterotypic cell-cell adhesion; negative regulation of macromolecule metabolic process; and negative regulation of protein kinase C signaling. Located in several cellular components, including cortical actin cytoskeleton; membrane raft; and ruffle. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.829
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYADM | NM_138373.5 | c.782A>C | p.Tyr261Ser | missense_variant | 3/3 | ENST00000391770.9 | NP_612382.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYADM | ENST00000391770.9 | c.782A>C | p.Tyr261Ser | missense_variant | 3/3 | 1 | NM_138373.5 | ENSP00000375650 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250392Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135282
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GnomAD4 exome AF: 0.00000206 AC: 3AN: 1459432Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2AN XY: 725590
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GnomAD4 genome Cov.: 32
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32
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 27, 2023 | The c.782A>C (p.Y261S) alteration is located in exon 2 (coding exon 1) of the MYADM gene. This alteration results from a A to C substitution at nucleotide position 782, causing the tyrosine (Y) at amino acid position 261 to be replaced by a serine (S). 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
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;D;.;.;.
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;M;M
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D
Polyphen
D;D;D;D;D
Vest4
MutPred
Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);
MVP
MPC
1.4
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at