1-6593401-TC-AG

Variant names:

• chr1-6593401-TC-AG
• NM_014851.4:c.1757_1758delGAinsCT
• KLHL21 p.Arg586Pro

Variant summary

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

The NM_014851.4(KLHL21):​c.1757_1758delGAinsCT​(p.Arg586Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: KLHL21 NM_014851.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.645
• Publications: 0 publications found

Genes affected

KLHL21 (HGNC:29041): (kelch like family member 21) Enables cullin family protein binding activity. Contributes to ubiquitin-protein transferase activity. Involved in chromosome passenger complex localization to spindle midzone; protein ubiquitination; and regulation of cytokinesis. Located in polar microtubule. Part of Cul3-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014851.4. 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
	KLHL21	NM_014851.4	MANE Select	c.1757_1758delGAinsCT	p.Arg586Pro	missense	N/A	NP_055666.2
	KLHL21	NM_001324309.2		c.*706_*707delGAinsCT		3_prime_UTR	Exon 4 of 4	NP_001311238.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL21	ENST00000377658.8	TSL:1 MANE Select	c.1757_1758delGAinsCT	p.Arg586Pro	missense	N/A	ENSP00000366886.4	Q9UJP4-1
	KLHL21	ENST00000496707.5	TSL:1	c.656_657delGAinsCT	p.Arg219Pro	missense	N/A	ENSP00000468710.1	K7ESH2
	KLHL21	ENST00000377663.3	TSL:1	c.*1963_*1964delGAinsCT		3_prime_UTR	Exon 3 of 3	ENSP00000366891.3	Q9UJP4-2

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.65

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-6653461;