NM_001375405.1:c.*247T>A

Variant names:

• chr5-123346272-A-T
• rs112271669
• NM_001375405.1:c.*247T>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001375405.1(CEP120):​c.*247T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00288 in 383,468 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0061 (8 hom., cov: 33)
  • Exomes 𝑓: 0.00074 (1 hom.)
• Consequence: CEP120 NM_001375405.1 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.555
• Publications: 1 publications found

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]

CEP120 Gene-Disease associations (from GenCC):

• ciliopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• Joubert syndrome 31

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• short-rib thoracic dysplasia 13 with or without polydactyly

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Jeune syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Joubert syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Joubert syndrome with ocular defect

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 5-123346272-A-T is Benign according to our data. Variant chr5-123346272-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1213615.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00614 (935/152326) while in subpopulation AFR AF = 0.0209 (871/41576). AF 95% confidence interval is 0.0198. There are 8 homozygotes in GnomAd4. There are 443 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375405.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP120	NM_001375405.1	MANE Select	c.*247T>A		3_prime_UTR	Exon 20 of 20	NP_001362334.1	Q8N960-1
	CEP120	NM_153223.4		c.*247T>A		3_prime_UTR	Exon 21 of 21	NP_694955.2	Q8N960-1
	CEP120	NM_001166226.2		c.*247T>A		3_prime_UTR	Exon 20 of 20	NP_001159698.1	Q8N960-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP120	ENST00000306467.10	TSL:5 MANE Select	c.*247T>A		3_prime_UTR	Exon 20 of 20	ENSP00000303058.6	Q8N960-1
	CEP120	ENST00000508138.5	TSL:1	n.*2780T>A		non_coding_transcript_exon	Exon 23 of 23	ENSP00000422234.1	D6R8Z4
	CEP120	ENST00000508138.5	TSL:1	n.*2780T>A		3_prime_UTR	Exon 23 of 23	ENSP00000422234.1	D6R8Z4

Frequencies

GnomAD3 genomes AF: 0.00613 AC: 933 AN: 152208 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.0210

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00347

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00479

GnomAD4 exome AF: 0.000735 AC: 170 AN: 231142 Hom.: 1 Cov.: 0 AF XY: 0.000609 AC XY: 73 AN XY: 119918

African (AFR) AF: 0.0187 AC: 120 AN: 6412

American (AMR) AF: 0.00192 AC: 16 AN: 8334

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8164

East Asian (EAS) AF: 0.00 AC: 0 AN: 17458

South Asian (SAS) AF: 0.00 AC: 0 AN: 13398

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14434

Middle Eastern (MID) AF: 0.000864 AC: 1 AN: 1158

European-Non Finnish (NFE) AF: 0.0000340 AC: 5 AN: 147260

Other (OTH) AF: 0.00193 AC: 28 AN: 14524

GnomAD4 genome AF: 0.00614 AC: 935 AN: 152326 Hom.: 8 Cov.: 33 AF XY: 0.00595 AC XY: 443 AN XY: 74476

African (AFR) AF: 0.0209 AC: 871 AN: 41576

American (AMR) AF: 0.00346 AC: 53 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68022

Other (OTH) AF: 0.00474 AC: 10 AN: 2110

Alfa AF: 0.00451 Hom.: 0

Bravo AF: 0.00680

Asia WGS AF: 0.00290 AC: 10 AN: 3468

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	9.0
DANN	Benign	0.83
PhyloP100		0.56
Mutation Taster		=100/0	polymorphism

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: rs112271669; hg19: chr5-122681966;