10-12203315-T-G

Variant names:

• chr10-12203315-T-G
• rs1317549
• NM_006023.3:c.146+4539T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006023.3(CDC123):​c.146+4539T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 152,134 control chromosomes in the GnomAD database, including 24,319 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.56 (24319 hom., cov: 33)
• Consequence: CDC123 NM_006023.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.158
• Publications: 11 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDC123	NM_006023.3	c.146+4539T>G		intron_variant	Intron 2 of 12	ENST00000281141.9	NP_006014.2
CDC123	XM_005252638.5	c.146+4539T>G		intron_variant	Intron 2 of 11		XP_005252695.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDC123	ENST00000281141.9	c.146+4539T>G		intron_variant	Intron 2 of 12	1	NM_006023.3	ENSP00000281141.4

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84635 AN: 152016 Hom.: 24305 Cov.: 33

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.696

Gnomad AMR AF: 0.630

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.586

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.557 AC: 84696 AN: 152134 Hom.: 24319 Cov.: 33 AF XY: 0.554 AC XY: 41205 AN XY: 74380

African (AFR) AF: 0.436 AC: 18099 AN: 41480

American (AMR) AF: 0.630 AC: 9624 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 2025 AN: 3472

East Asian (EAS) AF: 0.332 AC: 1724 AN: 5188

South Asian (SAS) AF: 0.507 AC: 2448 AN: 4824

European-Finnish (FIN) AF: 0.559 AC: 5919 AN: 10582

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.629 AC: 42785 AN: 67988

Other (OTH) AF: 0.590 AC: 1244 AN: 2108

Alfa AF: 0.604 Hom.: 15245

Bravo AF: 0.558

Asia WGS AF: 0.465 AC: 1618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.71
PhyloP100		-0.16
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1317549; hg19: chr10-12245314;