1-5863296-TCTTCGTTTTTGTC-T

Position:

• chr1-5863296-TCTTCGTTTTTGTC-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Moderate PM2 PP5_Moderate

The NM_015102.5(NPHP4):​c.4237_4249delGACAAAAACGAAG​(p.Asp1413fs) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NPHP4 NM_015102.5 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 7.56

Genes affected

NPHP4 (HGNC:19104): (nephrocystin 4) This gene encodes a protein involved in renal tubular development and function. This protein interacts with nephrocystin, and belongs to a multifunctional complex that is localized to actin- and microtubule-based structures. Mutations in this gene are associated with nephronophthisis type 4, a renal disease, and with Senior-Loken syndrome type 4, a combination of nephronophthisis and retinitis pigmentosa. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2014]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 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 0.0103 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-5863296-TCTTCGTTTTTGTC-T is Pathogenic according to our data. Variant chr1-5863296-TCTTCGTTTTTGTC-T is described in ClinVar as [Pathogenic]. Clinvar id is 2681745.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPHP4	NM_015102.5	c.4237_4249delGACAAAAACGAAG	p.Asp1413fs	frameshift_variant	30/30	ENST00000378156.9	NP_055917.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPHP4	ENST00000378156.9	c.4237_4249delGACAAAAACGAAG	p.Asp1413fs	frameshift_variant	30/30	1	NM_015102.5	ENSP00000367398.4
NPHP4	ENST00000378169.7	n.*3138_*3150delGACAAAAACGAAG		non_coding_transcript_exon_variant	27/27	1		ENSP00000367411.3
NPHP4	ENST00000489180.6	n.*2048_*2060delGACAAAAACGAAG		non_coding_transcript_exon_variant	33/33	2		ENSP00000423747.1
NPHP4	ENST00000378169.7	n.*3138_*3150delGACAAAAACGAAG		3_prime_UTR_variant	27/27	1		ENSP00000367411.3
NPHP4	ENST00000489180.6	n.*2048_*2060delGACAAAAACGAAG		3_prime_UTR_variant	33/33	2		ENSP00000423747.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Nephronophthisis 4 Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Precision Medicine Center, Zhengzhou University

Dec 01, 2023

PVS1,PM2_p,PM3 -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-5923356;