chr1-42733388-T-A

Variant names:

• chr1-42733388-T-A
• rs765727450
• NM_148960.3:c.*1698A>T

Variant summary

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

The NM_148960.3(CLDN19):​c.*1698A>T variant causes a 3 prime UTR 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: 32)
• Consequence: CLDN19 NM_148960.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0230
• Publications: 0 publications found

Genes affected

CLDN19 (HGNC:2040): (claudin 19) The product of this gene belongs to the claudin family. It plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity. Defects in this gene are the cause of hypomagnesemia renal with ocular involvement (HOMGO). HOMGO is a progressive renal disease characterized by primary renal magnesium wasting with hypomagnesemia, hypercalciuria and nephrocalcinosis associated with severe ocular abnormalities such as bilateral chorioretinal scars, macular colobomata, significant myopia and nystagmus. Alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jun 2010]

CLDN19 Gene-Disease associations (from GenCC):

• renal hypomagnesemia 5 with ocular involvement

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Orphanet, PanelApp Australia

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=-0.88).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_148960.3. 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
	CLDN19	NM_148960.3	MANE Select	c.*1698A>T		3_prime_UTR	Exon 5 of 5	NP_683763.2	Q8N6F1-1
	CLDN19	NM_001185117.2		c.*2374A>T		3_prime_UTR	Exon 3 of 3	NP_001172046.1	Q8N6F1-3
	CLDN19	NM_001123395.2		c.*2480A>T		3_prime_UTR	Exon 4 of 4	NP_001116867.1	Q8N6F1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDN19	ENST00000296387.6	TSL:2 MANE Select	c.*1698A>T		3_prime_UTR	Exon 5 of 5	ENSP00000296387.1	Q8N6F1-1
	CLDN19	ENST00000539749.5	TSL:2	c.*2374A>T		3_prime_UTR	Exon 3 of 3	ENSP00000443229.1	Q8N6F1-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.0
DANN	Benign	0.55
PhyloP100		0.023

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs765727450; hg19: chr1-43199059;