11-78173938-T-G

Variant names:

• chr11-78173938-T-G
• NM_001029859.3:c.617A>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001029859.3(KCTD21):​c.617A>C​(p.Lys206Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K206R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: KCTD21 NM_001029859.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.90

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCTD21	NM_001029859.3	c.617A>C	p.Lys206Thr	missense_variant	Exon 2 of 2	ENST00000340067.4	NP_001025030.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCTD21	ENST00000340067.4	c.617A>C	p.Lys206Thr	missense_variant	Exon 2 of 2	1	NM_001029859.3	ENSP00000339340.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461894 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.087
Eigen_PC	Benign	-0.011
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.081	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	0.69	N
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.49	N
REVEL	Uncertain	0.39
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.024	D
Polyphen		0.96	P
Vest4		0.54
MutPred		0.50		Loss of methylation at K206 (P = 0.0151);
MVP		0.84
MPC		1.1
ClinPred		0.83	D
GERP RS		3.5
Varity_R		0.073
gMVP		0.68

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-77884984;