19-53873674-G-A

Variant summary

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

The NM_138373.5(MYADM):​c.145G>A​(p.Val49Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

MYADM
NM_138373.5 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.569
Variant links:
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]

Genome browser will be placed here

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=0.09509599).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MYADMNM_138373.5 linkc.145G>A p.Val49Met missense_variant Exon 3 of 3 ENST00000391770.9 NP_612382.1 Q96S97A0A024R4N0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MYADMENST00000391770.9 linkc.145G>A p.Val49Met missense_variant Exon 3 of 3 1 NM_138373.5 ENSP00000375650.4 Q96S97

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251382
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135890
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000410
AC:
6
AN:
1461866
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
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:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.0000151

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 21, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.145G>A (p.V49M) alteration is located in exon 2 (coding exon 1) of the MYADM gene. This alteration results from a G to A substitution at nucleotide position 145, causing the valine (V) at amino acid position 49 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
14
DANN
Uncertain
0.99
DEOGEN2
Benign
0.023
T;T;T;.;T;T;T;T;.
Eigen
Benign
-0.78
Eigen_PC
Benign
-0.75
FATHMM_MKL
Benign
0.47
N
LIST_S2
Benign
0.79
.;.;T;T;T;.;.;.;T
M_CAP
Benign
0.0074
T
MetaRNN
Benign
0.095
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.7
.;L;.;.;L;L;L;L;.
PrimateAI
Uncertain
0.65
T
PROVEAN
Benign
-1.9
N;N;N;N;N;N;N;N;N
REVEL
Benign
0.030
Sift
Benign
0.14
T;T;T;T;T;T;T;T;T
Sift4G
Benign
0.14
T;T;T;T;T;T;T;T;T
Polyphen
0.094
.;B;.;.;B;B;B;B;.
Vest4
0.24, 0.27
MVP
0.030
MPC
0.44
ClinPred
0.12
T
GERP RS
-0.48
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.071
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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs755445108; hg19: chr19-54376928; API