11-78179683-A-G

Variant names:

• chr11-78179683-A-G
• rs230656
• NM_001029859.3:c.-29-5100T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001029859.3(KCTD21):​c.-29-5100T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 151,696 control chromosomes in the GnomAD database, including 23,921 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.56 (23921 hom., cov: 31)
• Consequence: KCTD21 NM_001029859.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.843
• Publications: 4 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCTD21	NM_001029859.3	c.-29-5100T>C		intron_variant	Intron 1 of 1	ENST00000340067.4	NP_001025030.1
KCTD21	XM_047426803.1	c.-855-1698T>C		intron_variant	Intron 1 of 2		XP_047282759.1
KCTD21	XM_006718517.3	c.-276-1698T>C		intron_variant	Intron 1 of 2		XP_006718580.1
KCTD21	XM_006718518.4	c.-29-5100T>C		intron_variant	Intron 1 of 1		XP_006718581.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCTD21	ENST00000340067.4	c.-29-5100T>C		intron_variant	Intron 1 of 1	1	NM_001029859.3	ENSP00000339340.3

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84552 AN: 151578 Hom.: 23907 Cov.: 31

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.750

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.589

Gnomad OTH AF: 0.569

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

GnomAD4 genome AF: 0.558 AC: 84607 AN: 151696 Hom.: 23921 Cov.: 31 AF XY: 0.558 AC XY: 41335 AN XY: 74132

African (AFR) AF: 0.458 AC: 18906 AN: 41294

American (AMR) AF: 0.657 AC: 10027 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.589 AC: 2043 AN: 3470

East Asian (EAS) AF: 0.644 AC: 3318 AN: 5156

South Asian (SAS) AF: 0.591 AC: 2844 AN: 4810

European-Finnish (FIN) AF: 0.512 AC: 5383 AN: 10504

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.590 AC: 40024 AN: 67894

Other (OTH) AF: 0.565 AC: 1192 AN: 2108

Alfa AF: 0.569 Hom.: 17462

Bravo AF: 0.564

Asia WGS AF: 0.575 AC: 2001 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.30
DANN	Benign	0.36
PhyloP100		-0.84
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs230656; hg19: chr11-77890729;