Variant rs879255558 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PP2PP3_StrongPP5

The NM_001031710.3(KLHL7):c.1115G>A(p.Arg372Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

KLHL7
NM_001031710.3 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:2

Conservation

PhyloP100: 9.60

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), KLHL7. . Gene score misZ 3.907 (greater than the threshold 3.09). Trascript score misZ 5.0301 (greater than threshold 3.09). GenCC has associacion of gene with PERCHING syndrome, retinitis pigmentosa 42, cold-induced sweating syndrome, retinitis pigmentosa.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.961

PP5

Variant 7-23165876-G-A is Pathogenic according to our data. Variant chr7-23165876-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 226130.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr7-23165876-G-A is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KLHL7	NM_001031710.3 linkuse as main transcript	c.1115G>A	p.Arg372Gln	missense_variant	8/11	ENST00000339077.10	NP_001026880.2
KLHL7	NM_018846.5 linkuse as main transcript	c.971G>A	p.Arg324Gln	missense_variant	8/11		NP_061334.4
KLHL7	NR_033328.2 linkuse as main transcript	n.1488G>A		non_coding_transcript_exon_variant	9/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHL7	ENST00000339077.10 linkuse as main transcript	c.1115G>A	p.Arg372Gln	missense_variant	8/11	1	NM_001031710.3	ENSP00000343273	P1	Q8IXQ5-1
KLHL7	ENST00000409689.5 linkuse as main transcript	c.971G>A	p.Arg324Gln	missense_variant	8/11	1		ENSP00000386263		Q8IXQ5-5
KLHL7	ENST00000521082.5 linkuse as main transcript	c.*1123G>A		3_prime_UTR_variant, NMD_transcript_variant	9/12	1		ENSP00000430351
KLHL7	ENST00000469576.1 linkuse as main transcript	n.2G>A		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461838

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PERCHING syndrome

Pathogenic:1

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

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.44

BayesDel_noAF

Pathogenic

0.40

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.38

T;.

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.96

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.92

D;D

M_CAP

Pathogenic

0.30

MetaRNN

Pathogenic

0.96

D;D

MetaSVM

Uncertain

0.70

MutationAssessor

Pathogenic

3.7

H;.

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Pathogenic

0.83

PROVEAN

Uncertain

-3.7

D;D

REVEL

Pathogenic

0.89

Sift

Uncertain

0.0010

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.74

MutPred

0.89

Gain of catalytic residue at R372 (P = 0.0344);.;

MVP

0.95

MPC

2.7

ClinPred

1.0

GERP RS

5.8

Varity_R

0.83

gMVP

0.95

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over