17-41854130-T-G

Position:

• chr17-41854130-T-G

Variant summary

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

The NM_018143.3(KLHL11):​c.1737A>C​(p.Lys579Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KLHL11 NM_018143.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.327

Genes affected

KLHL11 (HGNC:19008): (kelch like family member 11) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KLHL11 (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
KLHL11	NM_018143.3	c.1737A>C	p.Lys579Asn	missense_variant	2/2	ENST00000319121.4	NP_060613.1
KLHL11	XR_001752552.3	n.1790A>C		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHL11	ENST00000319121.4	c.1737A>C	p.Lys579Asn	missense_variant	2/2	1	NM_018143.3	ENSP00000314608.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 15, 2023

The c.1737A>C (p.K579N) alteration is located in exon 2 (coding exon 2) of the KLHL11 gene. This alteration results from a A to C substitution at nucleotide position 1737, causing the lysine (K) at amino acid position 579 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	2.0	M
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	0.29	N
REVEL	Benign	0.29
Sift	Benign	0.072	T
Sift4G	Uncertain	0.010	D
Polyphen		0.83	P
Vest4		0.63
MutPred		0.44		Loss of methylation at K579 (P = 0.0224);
MVP		0.69
MPC		1.3
ClinPred		0.66	D
GERP RS		1.9
Varity_R		0.33
gMVP		0.60

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

Other links and lift over

dbSNP: rs2048349450; hg19: chr17-40010382;