rs879255557

Variant names:

• chr7-23165779-AT-A
• rs879255557
• NM_001031710.3:c.1022delT

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_001031710.3(KLHL7):​c.1022delT​(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
• Publications: 1 publications found

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]

KLHL7 Gene-Disease associations (from GenCC):

• PERCHING syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Illumina, Ambry Genetics
• retinitis pigmentosa 42

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• cold-induced sweating syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Pathogenic. The variant received 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 VariationId is 226129.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031710.3. 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
	KLHL7	NM_001031710.3	MANE Select	c.1022delT	p.Leu341TrpfsTer9	frameshift	Exon 8 of 11	NP_001026880.2	Q8IXQ5-1
	KLHL7	NM_018846.5		c.878delT	p.Leu293TrpfsTer9	frameshift	Exon 8 of 11	NP_061334.4
	KLHL7	NR_033328.2		n.1395delT		non_coding_transcript_exon	Exon 9 of 12

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL7	ENST00000339077.10	TSL:1 MANE Select	c.1022delT	p.Leu341TrpfsTer9	frameshift	Exon 8 of 11	ENSP00000343273.4	Q8IXQ5-1
	KLHL7	ENST00000409689.5	TSL:1	c.878delT	p.Leu293TrpfsTer9	frameshift	Exon 8 of 11	ENSP00000386263.1	Q8IXQ5-5
	KLHL7	ENST00000521082.5	TSL:1	n.*1030delT		non_coding_transcript_exon	Exon 9 of 12	ENSP00000430351.1	E5RFN1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
2	-	-	PERCHING syndrome (2)
1	-	-	Cold-induced sweating syndrome 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.7
Mutation Taster		=0/200	disease causing (ClinVar)

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: rs879255557; hg19: chr7-23205398;