NM_138373.5:c.145G>T

Variant names:

• chr19-53873674-G-T
• rs755445108
• NM_138373.5:c.145G>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.145G>T​(p.Val49Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. V49M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYADM NM_138373.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.569
• 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=0.1293225).

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.145G>T	p.Val49Leu	missense	Exon 3 of 3	NP_612382.1	Q96S97
	MYADM	NM_001020818.2		c.145G>T	p.Val49Leu	missense	Exon 2 of 2	NP_001018654.1	Q96S97
	MYADM	NM_001020819.3		c.145G>T	p.Val49Leu	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.145G>T	p.Val49Leu	missense	Exon 3 of 3	ENSP00000375650.4	Q96S97
	MYADM	ENST00000391768.2	TSL:1	c.145G>T	p.Val49Leu	missense	Exon 2 of 2	ENSP00000375648.2	Q96S97
	MYADM	ENST00000391769.3	TSL:1	c.145G>T	p.Val49Leu	missense	Exon 3 of 3	ENSP00000375649.2	Q96S97

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	9.6
DANN	Uncertain	0.97
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.57
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.040
Sift	Benign	0.13	T
Sift4G	Benign	0.21	T
Polyphen		0.0020	B
Vest4		0.032
MutPred		0.54		Gain of helix (P = 0.0854)
MVP		0.030
MPC		0.37
ClinPred		0.18	T
GERP RS		-0.48
Varity_R		0.11
gMVP		0.46
Mutation Taster		=81/19	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: rs755445108; hg19: chr19-54376928;