19-53873938-G-T

Variant names:

• chr19-53873938-G-T
• rs1246716963
• NM_138373.5:c.409G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138373.5(MYADM):​c.409G>T​(p.Ala137Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A137T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MYADM NM_138373.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.56
• Publications: 0 publications found

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-AS2 (HGNC:40385): (MYADM antisense RNA 2)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22930428).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138373.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYADM	NM_138373.5	MANE Select	c.409G>T	p.Ala137Ser	missense	Exon 3 of 3	NP_612382.1	Q96S97
	MYADM	NM_001020818.2		c.409G>T	p.Ala137Ser	missense	Exon 2 of 2	NP_001018654.1	Q96S97
	MYADM	NM_001020819.3		c.409G>T	p.Ala137Ser	missense	Exon 3 of 3	NP_001018655.1	Q96S97

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYADM	ENST00000391770.9	TSL:1 MANE Select	c.409G>T	p.Ala137Ser	missense	Exon 3 of 3	ENSP00000375650.4	Q96S97
	MYADM	ENST00000391768.2	TSL:1	c.409G>T	p.Ala137Ser	missense	Exon 2 of 2	ENSP00000375648.2	Q96S97
	MYADM	ENST00000391769.3	TSL:1	c.409G>T	p.Ala137Ser	missense	Exon 3 of 3	ENSP00000375649.2	Q96S97

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458768 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725886

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.0000199 AC: 1 AN: 50350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111986

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 33

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.018	T
Eigen	Benign	0.031
Eigen_PC	Benign	0.073
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.6
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.093
Sift	Benign	0.042	D
Sift4G	Benign	0.31	T
Polyphen		0.39	B
Vest4		0.094
MutPred		0.56		Gain of disorder (P = 0.0245)
MVP		0.12
MPC		0.93
ClinPred		0.76	D
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.54
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs1246716963; hg19: chr19-54377192;