rs879255557

chr7-23165779-AT-A

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_001031710.3(KLHL7):c.1022del(p.Leu341TrpfsTer9) 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 (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: KLHL7 NM_001031710.3 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:3
• Conservation: PhyloP100: 7.67

Genes affected

KLHL7 (HGNC:15646): (kelch like family member 7) This gene encodes a BTB-Kelch-related protein. The encoded protein may be involved in protein degradation. Mutations in this gene have been associated with retinitis pigmentosa 42. [provided by RefSeq, Feb 2010]

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 7-23165779-AT-A is Pathogenic according to our data. Variant chr7-23165779-AT-A is described in ClinVar as [Pathogenic]. Clinvar id is 226129.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr7-23165779-AT-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLHL7	NM_001031710.3	c.1022del	p.Leu341TrpfsTer9	frameshift_variant	8/11	ENST00000339077.10
KLHL7	NM_018846.5	c.878del	p.Leu293TrpfsTer9	frameshift_variant	8/11
KLHL7	NR_033328.2	n.1395del		non_coding_transcript_exon_variant	9/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLHL7	ENST00000339077.10	c.1022del	p.Leu341TrpfsTer9	frameshift_variant	8/11	1	NM_001031710.3	P1
KLHL7	ENST00000409689.5	c.878del	p.Leu293TrpfsTer9	frameshift_variant	8/11	1
KLHL7	ENST00000521082.5	c.*1030del		3_prime_UTR_variant, NMD_transcript_variant	9/12	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:3

Revision: no assertion criteria provided

Submissions by phenotype

PERCHING syndrome Pathogenic:2

Pathogenic, no assertion criteria provided	research	Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	-	- -
Pathogenic, no assertion criteria provided	literature only	OMIM	Jan 09, 2020	- -

Cold-induced sweating syndrome 1 Pathogenic:1

Pathogenic, no assertion criteria provided

research

National Research Council, Institute of Genetics and Biomedical Research

Jan 01, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs879255557; hg19: chr7-23205398;