17-41864937-G-C

Position:

• chr17-41864937-G-C

Variant summary

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

The NM_018143.3(KLHL11):​c.434C>G​(p.Ser145Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KLHL11 NM_018143.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57

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.434C>G	p.Ser145Cys	missense_variant	1/2	ENST00000319121.4	NP_060613.1
KLHL11	XR_001752552.3	n.487C>G		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHL11	ENST00000319121.4	c.434C>G	p.Ser145Cys	missense_variant	1/2	1	NM_018143.3	ENSP00000314608.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Nov 10, 2022

The c.434C>G (p.S145C) alteration is located in exon 1 (coding exon 1) of the KLHL11 gene. This alteration results from a C to G substitution at nucleotide position 434, causing the serine (S) at amino acid position 145 to be replaced by a cysteine (C). 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	Benign	0.18
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	33
DANN	Benign	0.97
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.0050
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.77	T
M_CAP	Pathogenic	0.57	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	1.7	L
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.15	N
REVEL	Uncertain	0.30
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.0	B
Vest4		0.66
MutPred		0.40		Loss of phosphorylation at S145 (P = 0.0239);
MVP		0.76
MPC		0.80
ClinPred		0.88	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.20
gMVP		0.68

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: chr17-40021190;