5-123346640-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001375405.1(CEP120):c.2840G>A(p.Arg947His) variant causes a missense change. The variant allele was found at a frequency of 0.0363 in 1,613,692 control chromosomes in the GnomAD database, including 1,684 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R947C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.046 (216 hom., cov: 33)
  • Exomes 𝑓: 0.035 (1468 hom.)
• Consequence: CEP120 NM_001375405.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 6.51

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0030833483).
• BP6: Variant 5-123346640-C-T is Benign according to our data. Variant chr5-123346640-C-T is described in ClinVar as [Benign]. Clinvar id is 1168235.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.095 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP120	NM_001375405.1	c.2840G>A	p.Arg947His	missense_variant	20/20	ENST00000306467.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP120	ENST00000306467.10	c.2840G>A	p.Arg947His	missense_variant	20/20	5	NM_001375405.1	P1

Frequencies

GnomAD3 genomes AF: 0.0456 AC: 6930 AN: 152070 Hom.: 215 Cov.: 33

Gnomad AFR AF: 0.0465

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.0746

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.0913

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0551

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0310

Gnomad OTH AF: 0.0417

GnomAD3 exomes AF: 0.0533 AC: 13380 AN: 250998 Hom.: 533 AF XY: 0.0539 AC XY: 7311 AN XY: 135642

Gnomad AFR exome AF: 0.0462

Gnomad AMR exome AF: 0.0822

Gnomad ASJ exome AF: 0.0132

Gnomad EAS exome AF: 0.0893

Gnomad SAS exome AF: 0.101

Gnomad FIN exome AF: 0.0601

Gnomad NFE exome AF: 0.0297

Gnomad OTH exome AF: 0.0428

GnomAD4 exome AF: 0.0353 AC: 51630 AN: 1461504 Hom.: 1468 Cov.: 31 AF XY: 0.0372 AC XY: 27075 AN XY: 727034

Gnomad4 AFR exome AF: 0.0459

Gnomad4 AMR exome AF: 0.0824

Gnomad4 ASJ exome AF: 0.0130

Gnomad4 EAS exome AF: 0.0808

Gnomad4 SAS exome AF: 0.0994

Gnomad4 FIN exome AF: 0.0612

Gnomad4 NFE exome AF: 0.0256

Gnomad4 OTH exome AF: 0.0411

GnomAD4 genome AF: 0.0456 AC: 6943 AN: 152188 Hom.: 216 Cov.: 33 AF XY: 0.0486 AC XY: 3619 AN XY: 74394

Gnomad4 AFR AF: 0.0465

Gnomad4 AMR AF: 0.0744

Gnomad4 ASJ AF: 0.0141

Gnomad4 EAS AF: 0.0916

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.0551

Gnomad4 NFE AF: 0.0310

Gnomad4 OTH AF: 0.0450

Alfa AF: 0.0310 Hom.: 244

Bravo AF: 0.0444

TwinsUK AF: 0.0237 AC: 88

ALSPAC AF: 0.0234 AC: 90

ESP6500AA AF: 0.0515 AC: 227

ESP6500EA AF: 0.0280 AC: 241

ExAC AF: 0.0533 AC: 6468

Asia WGS AF: 0.111 AC: 387 AN: 3478

EpiCase AF: 0.0269

EpiControl AF: 0.0243

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 03, 2018

This variant is associated with the following publications: (PMID: 32772081) -

Short-rib thoracic dysplasia 13 with or without polydactyly Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.13
Cadd	Pathogenic	30
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.16	T;T;.
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.98	D
MetaRNN	Benign	0.0031	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M;M;.
MutationTaster	Benign	0.00010	P;P;P
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-3.4	D;D;D
REVEL	Benign	0.29
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.24
MPC		0.47
ClinPred		0.023	T
GERP RS		5.4
Varity_R		0.47
gMVP		0.53

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: rs2303720; hg19: chr5-122682334; COSMIC: COSV60264675; COSMIC: COSV60264675;