dbSNP rs977593432: MYADM:p.Gly131Ser (chr19-53873920-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_138373.5(MYADM):c.391G>A(p.Gly131Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,459,822 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: 0.0000055 ( 0 hom. )

Consequence

MYADM
NM_138373.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0850

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:

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=0.18095925).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYADM	NM_138373.5 link	c.391G>A	p.Gly131Ser	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
MYADM	ENST00000391770.9 link	c.391G>A	p.Gly131Ser	missense_variant	Exon 3 of 3	1	NM_138373.5	ENSP00000375650.4		Q96S97

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

249870

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135256

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000867

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:

0.00000548

AC:

AN:

1459822

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726352

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

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:

0.00000450

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

Oct 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.391G>A (p.G131S) 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 391, causing the glycine (G) at amino acid position 131 to be replaced by a serine (S). 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

0.19

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.046

T;T;T;.;T;T;T;T;.

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.69

.;.;T;T;T;.;.;.;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.18

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

.;L;.;.;L;L;L;L;.

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-2.6

D;D;D;D;D;D;D;D;D

REVEL

Benign

0.092

Sift

Benign

0.15

T;T;T;T;T;T;T;T;T

Sift4G

Benign

0.20

T;T;T;T;T;T;T;T;T

Polyphen

1.0

.;D;.;.;D;D;D;D;.

Vest4

0.087, 0.12

MutPred

0.48

Gain of glycosylation at G131 (P = 0.0178);Gain of glycosylation at G131 (P = 0.0178);Gain of glycosylation at G131 (P = 0.0178);Gain of glycosylation at G131 (P = 0.0178);Gain of glycosylation at G131 (P = 0.0178);Gain of glycosylation at G131 (P = 0.0178);Gain of glycosylation at G131 (P = 0.0178);Gain of glycosylation at G131 (P = 0.0178);Gain of glycosylation at G131 (P = 0.0178);

MVP

0.32

MPC

0.85

ClinPred

0.49

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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