NM_144711.6:c.189G>A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_144711.6(KLHL23):​c.189G>A​(p.Lys63Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,456,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: KLHL23 NM_144711.6 synonymous
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=2.53 with no splicing effect.

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>A	p.Lys63Lys	synonymous	Exon 2 of 4	NP_653312.2
	PHOSPHO2-KLHL23	NM_001199290.3		c.189G>A	p.Lys63Lys	synonymous	Exon 4 of 6	NP_001186219.1
	PHOSPHO2-KLHL23	NR_144936.2		n.359-6182G>A		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>A	p.Lys63Lys	synonymous	Exon 2 of 4	ENSP00000376419.2	Q8NBE8
	KLHL23	ENST00000272797.8	TSL:2	c.189G>A	p.Lys63Lys	synonymous	Exon 4 of 6	ENSP00000272797.4	Q8NBE8
	KLHL23	ENST00000919244.1		c.189G>A	p.Lys63Lys	synonymous	Exon 2 of 4	ENSP00000589303.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 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: 0.0000237 AC: 2 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: 0.00 AC: 0 AN: 1110730

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	9.7
DANN	Benign	0.58
PhyloP100		2.5
PromoterAI		-0.022	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=89/11	polymorphism

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;