Variant chr19-53874271-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000391770.9(MYADM):c.742G>A(p.Val248Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000048 in 1,457,236 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: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

MYADM
ENST00000391770.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.56

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]

MYADM links:

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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=0.3691551).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYADM	NM_138373.5 linkuse as main transcript	c.742G>A	p.Val248Ile	missense_variant	3/3	ENST00000391770.9	NP_612382.1	Q96S97A0A024R4N0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYADM	ENST00000391770.9 linkuse as main transcript	c.742G>A	p.Val248Ile	missense_variant	3/3	1	NM_138373.5	ENSP00000375650.4		Q96S97

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

248606

Hom.:

AF XY:

0.00000745

AC XY:

AN XY:

134250

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000873

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000480

AC:

AN:

1457236

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724236

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000135

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:

9.02e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

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

Jul 09, 2021

The c.742G>A (p.V248I) 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 742, causing the valine (V) at amino acid position 248 to be replaced by an isoleucine (I). 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

0.11

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.094

T;.;T;T;T;T

Eigen

Uncertain

0.29

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.79

.;T;T;.;.;.

M_CAP

Benign

0.011

MetaRNN

Benign

0.37

T;T;T;T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.6

M;.;M;M;M;M

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.67

N;N;N;N;N;N

REVEL

Benign

0.23

Sift

Benign

0.13

T;T;T;T;T;T

Sift4G

Benign

0.14

T;T;T;T;T;T

Polyphen

1.0

D;.;D;D;D;D

Vest4

0.36

MutPred

0.60

Loss of catalytic residue at V248 (P = 0.1165);Loss of catalytic residue at V248 (P = 0.1165);Loss of catalytic residue at V248 (P = 0.1165);Loss of catalytic residue at V248 (P = 0.1165);Loss of catalytic residue at V248 (P = 0.1165);Loss of catalytic residue at V248 (P = 0.1165);

MVP

0.13

MPC

0.63

ClinPred

0.35

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.044

gMVP

0.61

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over