21-37714359-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_002240.5(KCNJ6):​c.798G>A​(p.Thr266Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000182 in 1,614,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

KCNJ6
NM_002240.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.952
Variant links:
Genes affected
KCNJ6 (HGNC:6267): (potassium inwardly rectifying channel subfamily J member 6) This gene encodes a member of the G protein-coupled inwardly-rectifying potassium channel family of inward rectifier potassium channels. This type of potassium channel allows a greater flow of potassium into the cell than out of it. These proteins modulate many physiological processes, including heart rate in cardiac cells and circuit activity in neuronal cells, through G-protein coupled receptor stimulation. Mutations in this gene are associated with Keppen-Lubinsky Syndrome, a rare condition characterized by severe developmental delay, facial dysmorphism, and intellectual disability. [provided by RefSeq, Apr 2015]
KCNJ6-AS1 (HGNC:41352): (KCNJ6 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
Variant 21-37714359-C-T is Benign according to our data. Variant chr21-37714359-C-T is described in ClinVar as [Benign]. Clinvar id is 2155361.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.952 with no splicing effect.
BS2
High AC in GnomAd4 at 30 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KCNJ6NM_002240.5 linkc.798G>A p.Thr266Thr synonymous_variant 3/4 ENST00000609713.2 NP_002231.1 P48051
KCNJ6-AS1NR_183540.1 linkn.801C>T non_coding_transcript_exon_variant 4/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KCNJ6ENST00000609713.2 linkc.798G>A p.Thr266Thr synonymous_variant 3/41 NM_002240.5 ENSP00000477437.1 P48051
KCNJ6ENST00000645093.1 linkc.798G>A p.Thr266Thr synonymous_variant 4/5 ENSP00000493772.1 P48051

Frequencies

GnomAD3 genomes
AF:
0.000197
AC:
30
AN:
152128
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00347
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000337
AC:
84
AN:
249582
Hom.:
0
AF XY:
0.000288
AC XY:
39
AN XY:
135404
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000348
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00356
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000618
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.000181
AC:
264
AN:
1461878
Hom.:
0
Cov.:
32
AF XY:
0.000149
AC XY:
108
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000313
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00176
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000151
Gnomad4 OTH exome
AF:
0.000132
GnomAD4 genome
AF:
0.000197
AC:
30
AN:
152246
Hom.:
0
Cov.:
32
AF XY:
0.000201
AC XY:
15
AN XY:
74452
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00348
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.0000647
Hom.:
0
Bravo
AF:
0.000125
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

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 testingLabcorp Genetics (formerly Invitae), LabcorpMay 11, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.67
CADD
Benign
0.58
DANN
Benign
0.86

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: rs376122684; hg19: chr21-39086662; COSMIC: COSV99900773; COSMIC: COSV99900773; API