10-12230999-A-C

Position:

• chr10-12230999-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_006023.3(CDC123):​c.489+3A>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00234 in 1,601,592 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0023 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (11 hom.)
• Consequence: CDC123 NM_006023.3 splice_region, intron
• Scores: Splicing: ADA: 0.9987
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.39

Genes affected

CDC123 (HGNC:16827): (cell division cycle 123) Predicted to be involved in eukaryotic translation initiation factor 2 complex assembly and positive regulation of translational initiation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CDC123 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP6: Variant 10-12230999-A-C is Benign according to our data. Variant chr10-12230999-A-C is described in ClinVar as [Benign]. Clinvar id is 770762.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC123	NM_006023.3	c.489+3A>C		splice_region_variant, intron_variant		ENST00000281141.9	NP_006014.2
CDC123	XM_005252638.5	c.393+3A>C		splice_region_variant, intron_variant			XP_005252695.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC123	ENST00000281141.9	c.489+3A>C		splice_region_variant, intron_variant		1	NM_006023.3	ENSP00000281141.4

Frequencies

GnomAD3 genomes AF: 0.00225 AC: 343 AN: 152234 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000723

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00799

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00228

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00272 AC: 671 AN: 247006 Hom.: 5 AF XY: 0.00239 AC XY: 319 AN XY: 133548

Gnomad AFR exome AF: 0.000681

Gnomad AMR exome AF: 0.0105

Gnomad ASJ exome AF: 0.00502

Gnomad EAS exome AF: 0.00126

Gnomad SAS exome AF: 0.000272

Gnomad FIN exome AF: 0.000232

Gnomad NFE exome AF: 0.00183

Gnomad OTH exome AF: 0.00331

GnomAD4 exome AF: 0.00235 AC: 3404 AN: 1449240 Hom.: 11 Cov.: 28 AF XY: 0.00224 AC XY: 1613 AN XY: 720224

Gnomad4 AFR exome AF: 0.000332

Gnomad4 AMR exome AF: 0.0106

Gnomad4 ASJ exome AF: 0.00385

Gnomad4 EAS exome AF: 0.00230

Gnomad4 SAS exome AF: 0.000308

Gnomad4 FIN exome AF: 0.000376

Gnomad4 NFE exome AF: 0.00229

Gnomad4 OTH exome AF: 0.00270

GnomAD4 genome AF: 0.00230 AC: 351 AN: 152352 Hom.: 5 Cov.: 32 AF XY: 0.00221 AC XY: 165 AN XY: 74512

Gnomad4 AFR AF: 0.000721

Gnomad4 AMR AF: 0.00850

Gnomad4 ASJ AF: 0.00374

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.00103

Gnomad4 FIN AF: 0.000282

Gnomad4 NFE AF: 0.00228

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00215 Hom.: 0

Bravo AF: 0.00280

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 20, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	16
DANN	Benign	0.96

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.96
SpliceAI score (max)		0.69		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.69		Position offset: -3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs149366829; hg19: chr10-12272998;