11-78173865-G-T

Variant names:

• chr11-78173865-G-T
• NM_001029859.3:c.690C>A
• KCTD21 p.Ile230Ile

Variant summary

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

The NM_001029859.3(KCTD21):​c.690C>A​(p.Ile230Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. I230I) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: KCTD21 NM_001029859.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.25
• 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: 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=-0.78).
• BP7: Synonymous conserved (PhyloP=-3.25 with no splicing effect.

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.690C>A	p.Ile230Ile	synonymous	Exon 2 of 2	NP_001025030.1	Q4G0X4
	KCTD21-AS1	NR_102280.1		n.971G>T		non_coding_transcript_exon	Exon 4 of 4
	KCTD21-AS1	NR_102281.1		n.443G>T		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD21	ENST00000340067.4	TSL:1 MANE Select	c.690C>A	p.Ile230Ile	synonymous	Exon 2 of 2	ENSP00000339340.3	Q4G0X4
	KCTD21	ENST00000908679.1		c.690C>A	p.Ile230Ile	synonymous	Exon 3 of 3	ENSP00000578738.1
	KCTD21	ENST00000908680.1		c.690C>A	p.Ile230Ile	synonymous	Exon 2 of 2	ENSP00000578739.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.16
DANN	Benign	0.69
PhyloP100		-3.2

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

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

Other links and lift over

hg19: chr11-77884911;