rs61743233

Variant names:

• chr5-157472917-C-A
• rs61743233
• NM_001099287.2:c.1172C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-157472917-C-A
• chr5-157472917-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PVS1_Moderate PM2

The NM_001099287.2(NIPAL4):​c.1172C>A​(p.Ser391*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NIPAL4 NM_001099287.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.645
• Publications: 10 publications found

Genes affected

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]

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 4 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0354 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIPAL4	NM_001099287.2	c.1172C>A	p.Ser391*	stop_gained	Exon 6 of 6	ENST00000311946.8	NP_001092757.2
NIPAL4	NM_001172292.2	c.1115C>A	p.Ser372*	stop_gained	Exon 5 of 5		NP_001165763.2
NIPAL4	XM_011534552.2	c.863C>A	p.Ser288*	stop_gained	Exon 6 of 6		XP_011532854.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NIPAL4	ENST00000311946.8	c.1172C>A	p.Ser391*	stop_gained	Exon 6 of 6	1	NM_001099287.2	ENSP00000311687.8
NIPAL4	ENST00000435489.7	c.1115C>A	p.Ser372*	stop_gained	Exon 5 of 5	2		ENSP00000406456.3
ADAM19	ENST00000517951.5	n.*1741+15348G>T		intron_variant	Intron 21 of 22	2		ENSP00000428376.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000565 AC: 1 AN: 176962 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000450

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1372522 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 672700

African (AFR) AF: 0.00 AC: 0 AN: 30578

American (AMR) AF: 0.00 AC: 0 AN: 31116

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20282

East Asian (EAS) AF: 0.00 AC: 0 AN: 38946

South Asian (SAS) AF: 0.00 AC: 0 AN: 70902

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49798

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1069128

Other (OTH) AF: 0.00 AC: 0 AN: 56456

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000853 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.41
CADD	Pathogenic	35
DANN	Uncertain	0.99
Eigen	Uncertain	0.47
Eigen_PC	Benign	0.21
FATHMM_MKL	Benign	0.44	N
PhyloP100		0.65
Vest4		0.15
GERP RS		5.5
Mutation Taster		=25/175	disease causing

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: rs61743233; hg19: chr5-156899925;