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GeneBe

11-78173865-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001029859.3(KCTD21):c.690C>T(p.Ile230=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00174 in 1,614,148 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0077 ( 13 hom., cov: 31)
Exomes 𝑓: 0.0011 ( 11 hom. )

Consequence

KCTD21
NM_001029859.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.25
Variant links:
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)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-78173865-G-A is Benign according to our data. Variant chr11-78173865-G-A is described in ClinVar as [Benign]. Clinvar id is 778440.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.25 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00767 (1168/152268) while in subpopulation AFR AF= 0.0225 (935/41544). AF 95% confidence interval is 0.0213. There are 13 homozygotes in gnomad4. There are 565 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 13 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
KCTD21NM_001029859.3 linkuse as main transcriptc.690C>T p.Ile230= synonymous_variant 2/2 ENST00000340067.4
KCTD21-AS1NR_102280.1 linkuse as main transcriptn.971G>A non_coding_transcript_exon_variant 4/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
KCTD21ENST00000340067.4 linkuse as main transcriptc.690C>T p.Ile230= synonymous_variant 2/21 NM_001029859.3 P1
KCTD21-AS1ENST00000662186.1 linkuse as main transcriptn.873G>A non_coding_transcript_exon_variant 3/3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00765
AC:
1164
AN:
152150
Hom.:
13
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0225
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0136
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00154
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00574
GnomAD3 exomes
AF:
0.00357
AC:
898
AN:
251412
Hom.:
10
AF XY:
0.00271
AC XY:
368
AN XY:
135868
show subpopulations
Gnomad AFR exome
AF:
0.0214
Gnomad AMR exome
AF:
0.0144
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00141
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000880
Gnomad OTH exome
AF:
0.00195
GnomAD4 exome
AF:
0.00112
AC:
1633
AN:
1461880
Hom.:
11
Cov.:
32
AF XY:
0.000993
AC XY:
722
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.0228
Gnomad4 AMR exome
AF:
0.0138
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00116
Gnomad4 SAS exome
AF:
0.000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000728
Gnomad4 OTH exome
AF:
0.00187
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00767
AC:
1168
AN:
152268
Hom.:
13
Cov.:
31
AF XY:
0.00759
AC XY:
565
AN XY:
74458
show subpopulations
Gnomad4 AFR
AF:
0.0225
Gnomad4 AMR
AF:
0.0136
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00154
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00568
Alfa
AF:
0.00337
Hom.:
4
Bravo
AF:
0.00883
Asia WGS
AF:
0.00289
AC:
10
AN:
3478
EpiCase
AF:
0.000218
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJun 29, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
Cadd
Benign
0.66
Dann
Benign
0.75

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs80062567; hg19: chr11-77884911; API