Genetic Variant ADAM19:n.*1741+28117G>T (chr5-157460148-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000517951.5(ADAM19):n.*1741+28117G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000157 in 1,276,060 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: 0.0000016 ( 0 hom. )

Consequence

ADAM19
ENST00000517951.5 intron

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.68

Publications

0 publications found

Variant links:

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]

ADAM19 links:

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]

NIPAL4 links:

ENSG00000285868 (HGNC:):

ENSG00000285868 links:

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

NIPAL4-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.2041015).

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NIPAL4	NM_001099287.2	MANE Select	c.-173C>A	upstream_gene	N/A	NP_001092757.2	Q0D2K0-1
NIPAL4	NM_001172292.2		c.-173C>A	upstream_gene	N/A	NP_001165763.2	Q0D2K0-2
NIPAL4-DT	NR_136204.1		n.-48G>T	upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADAM19	ENST00000517951.5	TSL:2	n.*1741+28117G>T	intron	N/A	ENSP00000428376.1	E5RIS2
NIPAL4	ENST00000311946.8	TSL:1 MANE Select	c.-173C>A	upstream_gene	N/A	ENSP00000311687.8	Q0D2K0-1
ENSG00000285868	ENST00000519499.2	TSL:3	c.-2373G>T	upstream_gene	N/A	ENSP00000496943.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000157

AC:

AN:

1276060

Hom.:

Cov.:

AF XY:

0.00000162

AC XY:

AN XY:

618762

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24738

American (AMR)

AF:

0.00

AC:

AN:

17668

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17740

East Asian (EAS)

AF:

0.00

AC:

AN:

31002

South Asian (SAS)

AF:

0.0000332

AC:

AN:

60318

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4266

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1023642

Other (OTH)

AF:

0.00

AC:

AN:

52290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.044

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.57

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.38

MutationAssessor

Benign

0.81

PhyloP100

1.7

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.52

REVEL

Uncertain

0.37

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0030

Polyphen

0.82

Vest4

0.40

MutPred

0.10

Loss of glycosylation at S5 (P = 0.0128)

MVP

0.61

MPC

0.63

ClinPred

0.64

GERP RS

2.7

PromoterAI

-0.49

Neutral

(source)

Varity_R

0.16

gMVP

0.12

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over