rs748414601

Variant names:

• chr1-961447-C-A
• rs748414601
• NM_198317.3:c.262C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-961447-C-A
• chr1-961447-C-G
• chr1-961447-C-T

Variant summary

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

The NM_198317.3(KLHL17):​c.262C>A​(p.Arg88Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000548 in 1,459,948 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R88C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: KLHL17 NM_198317.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.60
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198317.3. 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
	KLHL17	NM_198317.3	MANE Select	c.262C>A	p.Arg88Ser	missense	Exon 2 of 12	NP_938073.1	Q6TDP4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL17	ENST00000338591.8	TSL:1 MANE Select	c.262C>A	p.Arg88Ser	missense	Exon 2 of 12	ENSP00000343930.3	Q6TDP4
	KLHL17	ENST00000887516.1		c.262C>A	p.Arg88Ser	missense	Exon 2 of 12	ENSP00000557575.1
	KLHL17	ENST00000955598.1		c.262C>A	p.Arg88Ser	missense	Exon 2 of 12	ENSP00000625657.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 240658 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000548 AC: 8 AN: 1459948 Hom.: 0 Cov.: 30 AF XY: 0.00000826 AC XY: 6 AN XY: 726258

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51860

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000720 AC: 8 AN: 1111796

Other (OTH) AF: 0.00 AC: 0 AN: 60356

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	0.70	N
PhyloP100		5.6
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.27
Sift	Benign	0.17	T
Sift4G	Benign	0.33	T
Polyphen		0.91	P
Vest4		0.79
MutPred		0.58		Loss of MoRF binding (P = 0.0174)
MVP		0.79
ClinPred		0.88	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.34
gMVP		0.54
Mutation Taster		=10/90	disease causing

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

Other links and lift over

dbSNP: rs748414601; hg19: chr1-896827;