rs8017603

Variant names:

• chr14-20435747-C-G
• rs8017603
• NM_001365790.2:c.65G>C

Your query was ambiguous. Multiple possible variants found:

• chr14-20435747-C-G
• chr14-20435747-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001365790.2(KLHL33):​c.65G>C​(p.Arg22Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 6/7 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
• Consequence: KLHL33 NM_001365790.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212
• Publications: 17 publications found

Genes affected

KLHL33 (HGNC:31952): (kelch like family member 33)

ENSG00000291038 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14852494).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365790.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL33	NM_001365790.2	MANE Select	c.65G>C	p.Arg22Thr	missense	Exon 2 of 5	NP_001352719.1	A0A1B0GUB7
	KLHL33	NM_001109997.3		c.-328G>C		5_prime_UTR	Exon 1 of 4	NP_001103467.2	A6NCF5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL33	ENST00000636854.3	TSL:5 MANE Select	c.65G>C	p.Arg22Thr	missense	Exon 2 of 5	ENSP00000490040.1	A0A1B0GUB7
	KLHL33	ENST00000637228.1	TSL:5	c.65G>C	p.Arg22Thr	missense	Exon 1 of 4	ENSP00000489731.1	A0A1B0GTK0
	ENSG00000291038	ENST00000800199.1		n.213-2113C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151788 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 39

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151788 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74106

African (AFR) AF: 0.0000242 AC: 1 AN: 41306

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5122

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67918

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 76980

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_noAF	Benign	-0.30
CADD	Benign	17
DANN	Benign	0.73
DEOGEN2	Benign	0.0070	T
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.34	T
MetaRNN	Benign	0.15	T
PhyloP100		0.21
GERP RS		4.3
PromoterAI		0.028	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8017603; hg19: chr14-20903906;