18-32770132-C-G

Position:

• chr18-32770132-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020805.3(KLHL14):​c.460G>C​(p.Val154Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as other (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: KLHL14 NM_020805.3 missense
• Clinical Significance: - - O:1
• Conservation: PhyloP100: 4.05

Genes affected

KLHL14 (HGNC:29266): (kelch like family member 14) The protein encoded by this gene is a member of the Kelch-like gene family, whose members contain a BTB/POZ domain, a BACK domain, and several Kelch domains. The encoded protein possesses six Kelch domains and localizes to the endoplasmic reticulum, where it interacts with torsin-1A. [provided by RefSeq, Sep 2015]

ENSG00000228835 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHL14	NM_020805.3	c.460G>C	p.Val154Leu	missense_variant	2/9	ENST00000359358.9	NP_065856.1
KLHL14	XM_047437684.1	c.460G>C	p.Val154Leu	missense_variant	2/4		XP_047293640.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHL14	ENST00000359358.9	c.460G>C	p.Val154Leu	missense_variant	2/9	1	NM_020805.3	ENSP00000352314.4
KLHL14	ENST00000358095.4	c.460G>C	p.Val154Leu	missense_variant	2/4	1		ENSP00000350808.4
KLHL14	ENST00000583263.1	c.541G>C	p.Val181Leu	missense_variant	2/2	2		ENSP00000463803.1
ENSG00000228835	ENST00000426194.1	n.173+165C>G		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 48

GnomAD4 genome Cov.: 31

ClinVar

Significance: -

Submissions summary: Other:1

Revision: -

Submissions by phenotype

Neoplasm Other:1

-, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Jul 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	24
DANN	Benign	0.95
DEOGEN2	Benign	0.24	T;.;T
Eigen	Benign	-0.064
Eigen_PC	Benign	0.082
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.51	D;D;D
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	0.81	L;L;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.3	N;N;.
REVEL	Benign	0.27
Sift	Benign	0.96	T;T;.
Sift4G	Benign	0.25	T;T;.
Polyphen		0.037	B;.;.
Vest4		0.40
MutPred		0.65		Gain of helix (P = 0.1736);Gain of helix (P = 0.1736);.;
MVP		0.67
MPC		0.43
ClinPred		0.78	D
GERP RS		4.3
Varity_R		0.22
gMVP		0.75

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-30350095;