2-224470712-CCT-C

Position:

• chr2-224470712-CCT-C

Variant summary

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

The NM_003590.5(CUL3):​c.*3531_*3532del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 231,806 control chromosomes in the GnomAD database, including 66 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (61 hom., cov: 33)
  • Exomes 𝑓: 0.0035 (5 hom.)
• Consequence: CUL3 NM_003590.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0490

Genes affected

CUL3 (HGNC:2553): (cullin 3) This gene encodes a member of the cullin protein family. The encoded protein plays a critical role in the polyubiquitination and subsequent degradation of specific protein substrates as the core component and scaffold protein of an E3 ubiquitin ligase complex. Complexes including the encoded protein may also play a role in late endosome maturation. Mutations in this gene are a cause of type 2E pseudohypoaldosteronism. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Mar 2012]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-224470712-CCT-C is Benign according to our data. Variant chr2-224470712-CCT-C is described in ClinVar as [Likely_benign]. Clinvar id is 334577.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CUL3	NM_003590.5	c.*3531_*3532del		3_prime_UTR_variant	16/16	ENST00000264414.9	NP_003581.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CUL3	ENST00000264414.9	c.*3531_*3532del		3_prime_UTR_variant	16/16	1	NM_003590.5	ENSP00000264414	P1
	ENST00000620050.1	n.242-3268_242-3267del		intron_variant, non_coding_transcript_variant		5
CUL3	ENST00000344951.8	c.*3531_*3532del		3_prime_UTR_variant	15/15	2		ENSP00000343601
	ENST00000622296.1	n.54-2214_54-2213del		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0154 AC: 2339 AN: 152134 Hom.: 61 Cov.: 33

Gnomad AFR AF: 0.0535

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00504

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0125

GnomAD4 exome AF: 0.00349 AC: 278 AN: 79554 Hom.: 5 AF XY: 0.00262 AC XY: 96 AN XY: 36582

Gnomad4 AFR exome AF: 0.0568

Gnomad4 AMR exome AF: 0.00647

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000180

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000163

Gnomad4 OTH exome AF: 0.00479

GnomAD4 genome AF: 0.0154 AC: 2343 AN: 152252 Hom.: 61 Cov.: 33 AF XY: 0.0152 AC XY: 1132 AN XY: 74444

Gnomad4 AFR AF: 0.0535

Gnomad4 AMR AF: 0.00503

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.00923 Hom.: 6

Bravo AF: 0.0174

Asia WGS AF: 0.00231 AC: 8 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autosomal dominant pseudohypoaldosteronism type 1 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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: rs10612010; hg19: chr2-225335429;