18-32769991-T-A

Position:

• chr18-32769991-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020805.3(KLHL14):​c.601A>T​(p.Thr201Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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: 4.96

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40505925).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHL14	NM_020805.3	c.601A>T	p.Thr201Ser	missense_variant	2/9	ENST00000359358.9	NP_065856.1
KLHL14	XM_047437684.1	c.601A>T	p.Thr201Ser	missense_variant	2/4		XP_047293640.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHL14	ENST00000359358.9	c.601A>T	p.Thr201Ser	missense_variant	2/9	1	NM_020805.3	ENSP00000352314.4
KLHL14	ENST00000358095.4	c.601A>T	p.Thr201Ser	missense_variant	2/4	1		ENSP00000350808.4
KLHL14	ENST00000583263.1	c.682A>T	p.???228???	splice_region_variant, synonymous_variant	2/2	2		ENSP00000463803.1
ENSG00000228835	ENST00000426194.1	n.173+24T>A		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	0.59
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	32
DANN	Uncertain	0.99
DEOGEN2	Benign	0.075	T;.
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.81	T;T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.41	T;T
MetaSVM	Benign	-0.30	T
MutationAssessor	Benign	0.85	L;L
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.4	N;N
REVEL	Uncertain	0.48
Sift	Uncertain	0.0070	D;T
Sift4G	Benign	0.076	T;D
Polyphen		0.41	B;.
Vest4		0.39
MutPred		0.66		Gain of disorder (P = 0.0562);Gain of disorder (P = 0.0562);
MVP		0.73
MPC		1.2
ClinPred		0.79	D
GERP RS		4.9
Varity_R		0.44
gMVP		0.49

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: chr18-30349954;