chr11-78174146-A-T

Variant names:

• chr11-78174146-A-T
• NM_001029859.3:c.409T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001029859.3(KCTD21):​c.409T>A​(p.Ser137Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: KCTD21 NM_001029859.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.89
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22757715).

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.409T>A	p.Ser137Thr	missense	Exon 2 of 2	NP_001025030.1	Q4G0X4
	KCTD21-AS1	NR_102280.1		n.*169A>T		downstream_gene	N/A
	KCTD21-AS1	NR_102281.1		n.*169A>T		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.409T>A	p.Ser137Thr	missense	Exon 2 of 2	ENSP00000339340.3	Q4G0X4
	KCTD21	ENST00000908679.1		c.409T>A	p.Ser137Thr	missense	Exon 3 of 3	ENSP00000578738.1
	KCTD21	ENST00000908680.1		c.409T>A	p.Ser137Thr	missense	Exon 2 of 2	ENSP00000578739.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

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	Benign	0.10
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.017
Eigen_PC	Benign	0.18
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		4.9
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.070
Sift	Benign	0.090	T
Sift4G	Benign	0.34	T
Polyphen		0.30	B
Vest4		0.37
MutPred		0.41		Loss of disorder (P = 0.04)
MVP		0.48
MPC		0.57
ClinPred		0.57	D
GERP RS		5.8
Varity_R		0.14
gMVP		0.65
Mutation Taster		=77/23	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

hg19: chr11-77885192;