11-78174198-ACG-GCA

Variant names:

• chr11-78174198-ACG-GCA
• NM_001029859.3:c.355_357delCGTinsTGC
• KCTD21 p.Arg119Cys

Variant summary

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

The NM_001029859.3(KCTD21):​c.355_357delCGTinsTGC​(p.Arg119Cys) 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: 31)
• Consequence: KCTD21 NM_001029859.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.78
• Publications: 0 publications found

Genes affected

KCTD21 (HGNC:27452): (potassium channel tetramerization domain containing 21) Enables cullin family protein binding activity; histone deacetylase binding activity; and identical protein binding activity. Involved in negative regulation of smoothened signaling pathway and ubiquitin-dependent protein catabolic process. [provided by Alliance of Genome Resources, Apr 2022]

KCTD21-AS1 (HGNC:48674): (KCTD21 antisense RNA 1)

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001029859.3. 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
	KCTD21	NM_001029859.3	MANE Select	c.355_357delCGTinsTGC	p.Arg119Cys	missense	N/A	NP_001025030.1	Q4G0X4
	KCTD21-AS1	NR_102280.1		n.*221_*223delACGinsGCA		downstream_gene	N/A
	KCTD21-AS1	NR_102281.1		n.*221_*223delACGinsGCA		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD21	ENST00000340067.4	TSL:1 MANE Select	c.355_357delCGTinsTGC	p.Arg119Cys	missense	N/A	ENSP00000339340.3	Q4G0X4
	KCTD21	ENST00000908679.1		c.355_357delCGTinsTGC	p.Arg119Cys	missense	N/A	ENSP00000578738.1
	KCTD21	ENST00000908680.1		c.355_357delCGTinsTGC	p.Arg119Cys	missense	N/A	ENSP00000578739.1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.8

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: chr11-77885244;