rs575762816

Variant names:

• chr19-53873918-A-C
• rs575762816
• NM_138373.5:c.389A>C

Your query was ambiguous. Multiple possible variants found:

• chr19-53873918-A-C
• chr19-53873918-A-G
• chr19-53873918-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138373.5(MYADM):​c.389A>C​(p.His130Pro) 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. 14/21 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. H130R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MYADM NM_138373.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440

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]

ACMG classification

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=0.10843304).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYADM	NM_138373.5	c.389A>C	p.His130Pro	missense_variant	Exon 3 of 3	ENST00000391770.9	NP_612382.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYADM	ENST00000391770.9	c.389A>C	p.His130Pro	missense_variant	Exon 3 of 3	1	NM_138373.5	ENSP00000375650.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	13
DANN	Benign	0.66
DEOGEN2	Benign	0.044	T;T;T;.;T;T;T;T;.
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.43	.;.;T;T;T;.;.;.;T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.11	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.95	.;L;.;.;L;L;L;L;.
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.8	D;D;D;D;D;D;D;D;D
REVEL	Benign	0.19
Sift	Benign	0.22	T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.22	T;T;T;T;T;T;T;T;T
Polyphen		0.016	.;B;.;.;B;B;B;B;.
Vest4		0.34, 0.34, 0.42
MutPred		0.39		Gain of glycosylation at H130 (P = 0.0972);Gain of glycosylation at H130 (P = 0.0972);Gain of glycosylation at H130 (P = 0.0972);Gain of glycosylation at H130 (P = 0.0972);Gain of glycosylation at H130 (P = 0.0972);Gain of glycosylation at H130 (P = 0.0972);Gain of glycosylation at H130 (P = 0.0972);Gain of glycosylation at H130 (P = 0.0972);Gain of glycosylation at H130 (P = 0.0972);
MVP		0.16
MPC		0.59
ClinPred		0.14	T
GERP RS		4.2
Varity_R		0.26
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

Other links and lift over

dbSNP: rs575762816; hg19: chr19-54377172; COSMIC: COSV61239867; COSMIC: COSV61239867;