10-12235993-C-T

Position:

• chr10-12235993-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006023.3(CDC123):​c.565+870C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 152,074 control chromosomes in the GnomAD database, including 15,615 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 0.43 (15615 hom., cov: 33)
• Consequence: CDC123 NM_006023.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.351

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC123	NM_006023.3	c.565+870C>T		intron_variant		ENST00000281141.9	NP_006014.2
CDC123	XM_005252638.5	c.469+870C>T		intron_variant			XP_005252695.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDC123	ENST00000281141.9	c.565+870C>T		intron_variant		1	NM_006023.3	ENSP00000281141	P1

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65601 AN: 151956 Hom.: 15605 Cov.: 33

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.642

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.432 AC: 65636 AN: 152074 Hom.: 15615 Cov.: 33 AF XY: 0.433 AC XY: 32219 AN XY: 74328

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.525

Gnomad4 ASJ AF: 0.496

Gnomad4 EAS AF: 0.338

Gnomad4 SAS AF: 0.471

Gnomad4 FIN AF: 0.496

Gnomad4 NFE AF: 0.524

Gnomad4 OTH AF: 0.472

Alfa AF: 0.499 Hom.: 22768

Bravo AF: 0.426

Asia WGS AF: 0.440 AC: 1532 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	7.5
DANN	Benign	0.85

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: rs7068966; hg19: chr10-12277992;