rs557034321

Variant names:

• chr5-157460192-C-A
• rs557034321
• ENST00000517951.5:n.*1741+28073G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-157460192-C-A
• chr5-157460192-C-T

Variant summary

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

The ENST00000517951.5(ADAM19):​n.*1741+28073G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000531 in 1,318,590 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000053 (0 hom.)
• Consequence: ADAM19 ENST00000517951.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.12
• 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]

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: 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=0.09822458).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIPAL4	NM_001099287.2	MANE Select	c.-129C>A		upstream_gene	N/A	NP_001092757.2	Q0D2K0-1
	NIPAL4	NM_001172292.2		c.-129C>A		upstream_gene	N/A	NP_001165763.2	Q0D2K0-2
	NIPAL4-DT	NR_136204.1		n.-92G>T		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM19	ENST00000517951.5	TSL:2	n.*1741+28073G>T		intron	N/A	ENSP00000428376.1	E5RIS2
	NIPAL4	ENST00000311946.8	TSL:1 MANE Select	c.-129C>A		upstream_gene	N/A	ENSP00000311687.8	Q0D2K0-1
	ENSG00000285868	ENST00000519499.2	TSL:3	c.-2417G>T		upstream_gene	N/A	ENSP00000496943.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000531 AC: 7 AN: 1318590 Hom.: 0 Cov.: 32 AF XY: 0.00000466 AC XY: 3 AN XY: 644318

African (AFR) AF: 0.00 AC: 0 AN: 26460

American (AMR) AF: 0.00 AC: 0 AN: 24206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19440

East Asian (EAS) AF: 0.00 AC: 0 AN: 32728

South Asian (SAS) AF: 0.00 AC: 0 AN: 65576

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45210

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4812

European-Non Finnish (NFE) AF: 0.00000669 AC: 7 AN: 1045888

Other (OTH) AF: 0.00 AC: 0 AN: 54270

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	17
DANN	Benign	0.94
DEOGEN2	Benign	0.040	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.065	D
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-0.32	T
MutationAssessor	Benign	0.90	L
PhyloP100		2.1
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.26
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.61	T
Polyphen		0.24	B
Vest4		0.21
MutPred		0.10		Loss of catalytic residue at P19 (P = 0.0144)
MVP		0.37
MPC		0.43
ClinPred		0.29	T
GERP RS		2.6
PromoterAI		-0.34	Neutral
Varity_R		0.073
gMVP		0.13

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: rs557034321; hg19: chr5-156887200;