chr1-111775819-A-AC

Position:

• chr1-111775819-A-AC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001378969.1(KCND3):​c.*257_*258insG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0445 in 98,172 control chromosomes in the GnomAD database, including 314 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.043 (53 hom., cov: 25)
  • Exomes 𝑓: 0.051 (261 hom.)
• Consequence: KCND3 NM_001378969.1 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.201

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 1-111775819-A-AC is Benign according to our data. Variant chr1-111775819-A-AC is described in ClinVar as [Likely_benign]. Clinvar id is 1210683.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.053 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCND3	NM_001378969.1	c.*257_*258insG		3_prime_UTR_variant	8/8	ENST00000302127.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCND3	ENST00000302127.5	c.*257_*258insG		3_prime_UTR_variant	8/8	5	NM_001378969.1	P3
KCND3	ENST00000315987.6	c.*257_*258insG		3_prime_UTR_variant	8/8	1		P3
KCND3	ENST00000369697.5	c.*257_*258insG		3_prime_UTR_variant	6/6	1		A1

Frequencies

GnomAD3 genomes AF: 0.0428 AC: 3346 AN: 78118 Hom.: 53 Cov.: 25

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.0314

Gnomad AMR AF: 0.0520

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.000402

Gnomad SAS AF: 0.00976

Gnomad FIN AF: 0.0558

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0549

Gnomad OTH AF: 0.0464

GnomAD4 exome AF: 0.0509 AC: 1019 AN: 20028 Hom.: 261 Cov.: 0 AF XY: 0.0498 AC XY: 529 AN XY: 10626

Gnomad4 AFR exome AF: 0.0718

Gnomad4 AMR exome AF: 0.0525

Gnomad4 ASJ exome AF: 0.0584

Gnomad4 EAS exome AF: 0.0432

Gnomad4 SAS exome AF: 0.0402

Gnomad4 FIN exome AF: 0.0521

Gnomad4 NFE exome AF: 0.0517

Gnomad4 OTH exome AF: 0.0649

GnomAD4 genome AF: 0.0428 AC: 3348 AN: 78144 Hom.: 53 Cov.: 25 AF XY: 0.0424 AC XY: 1562 AN XY: 36854

Gnomad4 AFR AF: 0.0130

Gnomad4 AMR AF: 0.0518

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.000402

Gnomad4 SAS AF: 0.00978

Gnomad4 FIN AF: 0.0558

Gnomad4 NFE AF: 0.0549

Gnomad4 OTH AF: 0.0460

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 02, 2018

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs72548738; hg19: chr1-112318441;