Variant rs15775 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3_Moderate

The NM_001031710.3(KLHL7):c.352C>A(p.Leu118Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L118L) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Consequence

KLHL7
NM_001031710.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.43

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 Uncertain_significance. Variant got 5 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, 0.864

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLHL7	NM_001031710.3 linkuse as main transcript	c.352C>A	p.Leu118Met	missense_variant	4/11	ENST00000339077.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLHL7	ENST00000339077.10 linkuse as main transcript	c.352C>A	p.Leu118Met	missense_variant	4/11	1	NM_001031710.3	P1	Q8IXQ5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.79

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.11

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.36

T;.;.;.

Eigen

Benign

0.18

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.96

D;D;D;D

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.86

D;D;D;D

MetaSVM

Uncertain

0.24

MutationAssessor

Benign

1.9

L;L;.;.

MutationTaster

Benign

0.0033

P;P;P;P;P;P;P;P;P

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-1.7

N;N;N;N

REVEL

Pathogenic

0.66

Sift

Benign

0.085

T;D;T;D

Sift4G

Benign

0.17

T;D;T;D

Polyphen

0.78

P;D;.;D

Vest4

0.64

MutPred

0.75

Gain of catalytic residue at V114 (P = 0.0301);Gain of catalytic residue at V114 (P = 0.0301);.;.;

MVP

0.78

MPC

1.9

ClinPred

0.93

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.23

gMVP

0.72

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over