rs1688480972

Variant names:

• chr2-169735203-G-T
• rs1688480972
• NM_144711.6:c.189G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-169735203-G-T
• chr2-169735203-G-A

Variant summary

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

The NM_144711.6(KLHL23):​c.189G>T​(p.Lys63Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,192 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: KLHL23 NM_144711.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.53
• Publications: 0 publications found

Genes affected

KLHL23 (HGNC:27506): (kelch like family member 23)

PHOSPHO2-KLHL23 (HGNC:):

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_144711.6. 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
	KLHL23	NM_144711.6	MANE Select	c.189G>T	p.Lys63Asn	missense	Exon 2 of 4	NP_653312.2
	PHOSPHO2-KLHL23	NM_001199290.3		c.189G>T	p.Lys63Asn	missense	Exon 4 of 6	NP_001186219.1
	PHOSPHO2-KLHL23	NR_144936.2		n.359-6182G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL23	ENST00000392647.7	TSL:1 MANE Select	c.189G>T	p.Lys63Asn	missense	Exon 2 of 4	ENSP00000376419.2	Q8NBE8
	KLHL23	ENST00000272797.8	TSL:2	c.189G>T	p.Lys63Asn	missense	Exon 4 of 6	ENSP00000272797.4	Q8NBE8
	KLHL23	ENST00000919244.1		c.189G>T	p.Lys63Asn	missense	Exon 2 of 4	ENSP00000589303.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456192 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 723988

African (AFR) AF: 0.00 AC: 0 AN: 33092

American (AMR) AF: 0.00 AC: 0 AN: 43524

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25924

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.00 AC: 0 AN: 84246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53126

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110730

Other (OTH) AF: 0.00 AC: 0 AN: 60150

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000370 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
Eigen	Benign	0.072
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.5
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.19
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.055	T
Polyphen		0.20	B
Vest4		0.60
MutPred		0.68		Loss of methylation at K63 (P = 0.0023)
MVP		0.71
MPC		0.48
ClinPred		0.89	D
GERP RS		3.7
PromoterAI		-0.080	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.49
gMVP		0.66
Mutation Taster		=50/50

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: rs1688480972; hg19: chr2-170591713;