Variant 1-111775852-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001378969.1(KCND3):c.*225T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 6 hom., cov: 16)

Exomes 𝑓: 0.0096 ( 4 hom. )

Consequence

KCND3
NM_001378969.1 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.460

Variant links:

Genes affected

KCND3 (HGNC:6239): (potassium voltage-gated channel subfamily D member 3) Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shal-related subfamily, members of which form voltage-activated A-type potassium ion channels and are prominent in the repolarization phase of the action potential. This member includes two isoforms with different sizes, which are encoded by alternatively spliced transcript variants of this gene. [provided by RefSeq, Jul 2008]

KCND3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 1-111775852-A-G is Benign according to our data. Variant chr1-111775852-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1197975.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0143 (940/65654) while in subpopulation NFE AF= 0.0174 (629/36054). AF 95% confidence interval is 0.0163. There are 6 homozygotes in gnomad4. There are 482 alleles in male gnomad4 subpopulation. Median coverage is 16. This position pass quality control queck.

BS2

High AC in GnomAd4 at 940 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCND3	NM_001378969.1 linkuse as main transcript	c.*225T>C		3_prime_UTR_variant	8/8	ENST00000302127.5	NP_001365898.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KCND3	ENST00000302127 linkuse as main transcript	c.*225T>C	3_prime_UTR_variant	8/8	5	NM_001378969.1	ENSP00000306923.4	Q9UK17-1
KCND3	ENST00000315987 linkuse as main transcript	c.*225T>C	3_prime_UTR_variant	8/8	1		ENSP00000319591.2	Q9UK17-1
KCND3	ENST00000369697 linkuse as main transcript	c.*225T>C	3_prime_UTR_variant	6/6	1		ENSP00000358711.1	Q9UK17-2

Frequencies

GnomAD3 genomes

AF:

0.0143

AC:

940

AN:

65630

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00315

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0103

Gnomad ASJ

AF:

0.00641

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00406

Gnomad FIN

AF:

0.0798

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0174

Gnomad OTH

AF:

0.00937

GnomAD4 exome

AF:

0.00959

AC:

406

AN:

42322

Hom.:

Cov.:

AF XY:

0.00842

AC XY:

197

AN XY:

23406

show subpopulations

Gnomad4 AFR exome

AF:

0.00238

Gnomad4 AMR exome

AF:

0.00428

Gnomad4 ASJ exome

AF:

0.00461

Gnomad4 EAS exome

AF:

0.000380

Gnomad4 SAS exome

AF:

0.00215

Gnomad4 FIN exome

AF:

0.0268

Gnomad4 NFE exome

AF:

0.0140

Gnomad4 OTH exome

AF:

0.0105

GnomAD4 genome

AF:

0.0143

AC:

940

AN:

65654

Hom.:

Cov.:

AF XY:

0.0155

AC XY:

482

AN XY:

31014

show subpopulations

Gnomad4 AFR

AF:

0.00315

Gnomad4 AMR

AF:

0.0103

Gnomad4 ASJ

AF:

0.00641

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00406

Gnomad4 FIN

AF:

0.0798

Gnomad4 NFE

AF:

0.0174

Gnomad4 OTH

AF:

0.00930

Alfa

AF:

0.00838

Hom.:

Bravo

AF:

0.00481

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 28, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.64

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over