5-157509354-A-C

Variant names:

• chr5-157509354-A-C
• rs2113725888
• NM_033274.5:c.852T>G
• ADAM19 p.Ser284Arg

Variant summary

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

The NM_033274.5(ADAM19):​c.852T>G​(p.Ser284Arg) 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. 15/24 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. S284C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: ADAM19 NM_033274.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.728
• Publications: 0 publications found

Genes affected

ADAM19 (HGNC:197): (ADAM metallopeptidase domain 19) This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. This member is a type I transmembrane protein and serves as a marker for dendritic cell differentiation. It has been demonstrated to be an active metalloproteinase, which may be involved in normal physiological processes such as cell migration, cell adhesion, cell-cell and cell-matrix interactions, and signal transduction. It is proposed to play a role in pathological processes, such as cancer, inflammatory diseases, renal diseases, and Alzheimer's disease. [provided by RefSeq, May 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033274.5. 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
	ADAM19	NM_033274.5	MANE Select	c.852T>G	p.Ser284Arg	missense	Exon 9 of 23	NP_150377.1	Q9H013-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM19	ENST00000257527.9	TSL:1 MANE Select	c.852T>G	p.Ser284Arg	missense	Exon 9 of 23	ENSP00000257527.5	Q9H013-2
	ADAM19	ENST00000517905.1	TSL:5	c.852T>G	p.Ser284Arg	missense	Exon 9 of 22	ENSP00000428654.1	Q9H013-1
	ADAM19	ENST00000957644.1		c.852T>G	p.Ser284Arg	missense	Exon 9 of 23	ENSP00000627703.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	13
DANN	Benign	0.85
DEOGEN2	Benign	0.052	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.60	N
PhyloP100		-0.73
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.053
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.030	D
Varity_R		0.15
gMVP		0.50
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.25		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2113725888; hg19: chr5-156936362;