1-960793-C-G

Variant names:

• chr1-960793-C-G
• rs1236359939
• NM_198317.3:c.100C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198317.3(KLHL17):​c.100C>G​(p.Pro34Ala) 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 benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P34S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: KLHL17 NM_198317.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.40

Genes affected

KLHL17 (HGNC:24023): (kelch like family member 17) The protein encoded by this gene is expressed in neurons of most regions of the brain. It contains an N-terminal BTB domain, which mediates dimerization of the protein, and a C-terminal Kelch domain, which mediates binding to F-actin. This protein may play a key role in the regulation of actin-based neuronal function. [provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12670654).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL17	NM_198317.3	c.100C>G	p.Pro34Ala	missense_variant	Exon 1 of 12	ENST00000338591.8	NP_938073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL17	ENST00000338591.8	c.100C>G	p.Pro34Ala	missense_variant	Exon 1 of 12	1	NM_198317.3	ENSP00000343930.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 18

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.027	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.28	T
M_CAP	Pathogenic	0.71	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.34	N
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	0.060	N
REVEL	Benign	0.068
Sift	Benign	0.13	T
Sift4G	Benign	0.66	T
Polyphen		0.0	B
Vest4		0.17
MutPred		0.30		Loss of catalytic residue at P34 (P = 0.0058);
MVP		0.33
ClinPred		0.080	T
GERP RS		0.29
Varity_R		0.062
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1236359939; hg19: chr1-896173;