5-123346654-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001375405.1(CEP120):c.2826T>C(p.Asp942=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.703 in 1,613,262 control chromosomes in the GnomAD database, including 399,949 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.72 (38994 hom., cov: 31)
  • Exomes 𝑓: 0.70 (360955 hom.)
• Consequence: CEP120 NM_001375405.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.325

Genes affected

CEP120 (HGNC:26690): (centrosomal protein 120) This gene encodes a protein that functions in the microtubule-dependent coupling of the nucleus and the centrosome. A similar protein in mouse plays a role in both interkinetic nuclear migration, which is a characteristic pattern of nuclear movement in neural progenitors, and in neural progenitor self-renewal. Mutations in this gene are predicted to result in neurogenic defects. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 5-123346654-A-G is Benign according to our data. Variant chr5-123346654-A-G is described in ClinVar as [Benign]. Clinvar id is 1167916.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.325 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP120	NM_001375405.1	c.2826T>C	p.Asp942=	synonymous_variant	20/20	ENST00000306467.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP120	ENST00000306467.10	c.2826T>C	p.Asp942=	synonymous_variant	20/20	5	NM_001375405.1	P1

Frequencies

GnomAD3 genomes AF: 0.715 AC: 108573 AN: 151868 Hom.: 38947 Cov.: 31

Gnomad AFR AF: 0.749

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.712

Gnomad ASJ AF: 0.736

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.708

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.746

GnomAD3 exomes AF: 0.690 AC: 173191 AN: 250918 Hom.: 60222 AF XY: 0.692 AC XY: 93881 AN XY: 135594

Gnomad AFR exome AF: 0.754

Gnomad AMR exome AF: 0.634

Gnomad ASJ exome AF: 0.734

Gnomad EAS exome AF: 0.575

Gnomad SAS exome AF: 0.667

Gnomad FIN exome AF: 0.711

Gnomad NFE exome AF: 0.714

Gnomad OTH exome AF: 0.706

GnomAD4 exome AF: 0.702 AC: 1025252 AN: 1461276 Hom.: 360955 Cov.: 49 AF XY: 0.700 AC XY: 509193 AN XY: 726908

Gnomad4 AFR exome AF: 0.751

Gnomad4 AMR exome AF: 0.646

Gnomad4 ASJ exome AF: 0.730

Gnomad4 EAS exome AF: 0.551

Gnomad4 SAS exome AF: 0.668

Gnomad4 FIN exome AF: 0.711

Gnomad4 NFE exome AF: 0.709

Gnomad4 OTH exome AF: 0.704

GnomAD4 genome AF: 0.715 AC: 108678 AN: 151986 Hom.: 38994 Cov.: 31 AF XY: 0.712 AC XY: 52857 AN XY: 74260

Gnomad4 AFR AF: 0.750

Gnomad4 AMR AF: 0.712

Gnomad4 ASJ AF: 0.736

Gnomad4 EAS AF: 0.574

Gnomad4 SAS AF: 0.665

Gnomad4 FIN AF: 0.708

Gnomad4 NFE AF: 0.708

Gnomad4 OTH AF: 0.747

Alfa AF: 0.714 Hom.: 75207

Bravo AF: 0.719

Asia WGS AF: 0.663 AC: 2304 AN: 3478

EpiCase AF: 0.725

EpiControl AF: 0.721

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Short-rib thoracic dysplasia 13 with or without polydactyly Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 22, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Joubert syndrome 31 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	4.3
Dann	Benign	0.49

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: rs1047438; hg19: chr5-122682348; COSMIC: COSV60264728; COSMIC: COSV60264728;