chr5-157460205-A-T

Variant names:

• chr5-157460205-A-T
• rs1754049246
• ENST00000517951.5:n.*1741+28060T>A

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+28060T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000752 in 1,328,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: ADAM19 ENST00000517951.5 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.558
• 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=0.24272963).

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.-116A>T		upstream_gene	N/A	NP_001092757.2	Q0D2K0-1
	NIPAL4	NM_001172292.2		c.-116A>T		upstream_gene	N/A	NP_001165763.2	Q0D2K0-2
	NIPAL4-DT	NR_136204.1		n.-105T>A		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM19	ENST00000517951.5	TSL:2	n.*1741+28060T>A		intron	N/A	ENSP00000428376.1	E5RIS2
	NIPAL4	ENST00000311946.8	TSL:1 MANE Select	c.-116A>T		upstream_gene	N/A	ENSP00000311687.8	Q0D2K0-1
	ENSG00000285868	ENST00000519499.2	TSL:3	c.-2430T>A		upstream_gene	N/A	ENSP00000496943.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.52e-7 AC: 1 AN: 1328960 Hom.: 0 Cov.: 32 AF XY: 0.00000154 AC XY: 1 AN XY: 650542

African (AFR) AF: 0.00 AC: 0 AN: 26940

American (AMR) AF: 0.00 AC: 0 AN: 25774

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20178

East Asian (EAS) AF: 0.00 AC: 0 AN: 32874

South Asian (SAS) AF: 0.00 AC: 0 AN: 67344

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4734

European-Non Finnish (NFE) AF: 9.52e-7 AC: 1 AN: 1050772

Other (OTH) AF: 0.00 AC: 0 AN: 54756

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Uncertain	0.085	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	16
DANN	Uncertain	0.97
DEOGEN2	Benign	0.048	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.48	T
M_CAP	Pathogenic	0.41	D
MetaRNN	Benign	0.24	T
MetaSVM	Uncertain	-0.098	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.56
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.72	N
REVEL	Uncertain	0.40
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.69	P
Vest4		0.27
MutPred		0.11		Loss of glycosylation at P20 (P = 0.1402)
MVP		0.43
MPC		0.44
ClinPred		0.35	T
GERP RS		2.5
PromoterAI		0.47	Neutral
Varity_R		0.13
gMVP		0.14

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: rs1754049246; hg19: chr5-156887213;