5-157460125-A-C

Variant names:

• chr5-157460125-A-C
• rs1105282
• ENST00000517951.5:n.*1741+28140T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000517951.5(ADAM19):​n.*1741+28140T>G variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADAM19 ENST00000517951.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.658
• Publications: 18 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]

NIPAL4 (HGNC:28018): (NIPA like domain containing 4) This gene likely encodes a membrane receptor. Mutations in this gene have been associated with autosomal recessive congenital ichthyosis. [provided by RefSeq, Feb 2010]

ENSG00000285868 (HGNC:):

NIPAL4-DT (HGNC:55542): (NIPAL4 divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000517951.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIPAL4	NM_001099287.2	MANE Select	c.-196A>C		upstream_gene	N/A	NP_001092757.2
	NIPAL4	NM_001172292.2		c.-196A>C		upstream_gene	N/A	NP_001165763.2
	NIPAL4-DT	NR_136204.1		n.-25T>G		upstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM19	ENST00000517951.5	TSL:2	n.*1741+28140T>G		intron	N/A	ENSP00000428376.1
	NIPAL4	ENST00000311946.8	TSL:1 MANE Select	c.-196A>C		upstream_gene	N/A	ENSP00000311687.8
	ENSG00000285868	ENST00000519499.2	TSL:3	c.-2350T>G		upstream_gene	N/A	ENSP00000496943.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1259388 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 610074

African (AFR) AF: 0.00 AC: 0 AN: 24194

American (AMR) AF: 0.00 AC: 0 AN: 15858

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17440

East Asian (EAS) AF: 0.00 AC: 0 AN: 30418

South Asian (SAS) AF: 0.00 AC: 0 AN: 59056

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44118

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3908

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1012788

Other (OTH) AF: 0.00 AC: 0 AN: 51608

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	11
DANN	Benign	0.70
PhyloP100		0.66
PromoterAI		-0.49	Neutral

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: rs1105282; hg19: chr5-156887133;