NM_001353108.3:c.783A>G

Variant names:

• chr3-134545813-A-G
• rs1278502113
• NM_001353108.3:c.783A>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001353108.3(CEP63):​c.783A>G​(p.Leu261Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000055 in 1,455,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: CEP63 NM_001353108.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.130
• Publications: 0 publications found

Genes affected

CEP63 (HGNC:25815): (centrosomal protein 63) This gene encodes a protein with six coiled-coil domains. The protein is localized to the centrosome, a non-membraneous organelle that functions as the major microtubule-organizing center in animal cells. Several alternatively spliced transcript variants have been found, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

CEP63 Gene-Disease associations (from GenCC):

• Seckel syndrome 6

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• autosomal recessive primary microcephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000288700 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 3-134545813-A-G is Benign according to our data. Variant chr3-134545813-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 434747.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.13 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353108.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP63	NM_001353108.3	MANE Select	c.783A>G	p.Leu261Leu	synonymous	Exon 7 of 15	NP_001340037.1
	CEP63	NM_025180.5		c.783A>G	p.Leu261Leu	synonymous	Exon 8 of 16	NP_079456.2
	CEP63	NM_001353109.1		c.783A>G	p.Leu261Leu	synonymous	Exon 7 of 14	NP_001340038.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP63	ENST00000675561.1	MANE Select	c.783A>G	p.Leu261Leu	synonymous	Exon 7 of 15	ENSP00000502085.1
	CEP63	ENST00000383229.8	TSL:1	c.783A>G	p.Leu261Leu	synonymous	Exon 7 of 13	ENSP00000372716.3
	CEP63	ENST00000332047.10	TSL:1	c.783A>G	p.Leu261Leu	synonymous	Exon 7 of 12	ENSP00000328382.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000550 AC: 8 AN: 1455806 Hom.: 0 Cov.: 29 AF XY: 0.00000690 AC XY: 5 AN XY: 724474

African (AFR) AF: 0.00 AC: 0 AN: 33272

American (AMR) AF: 0.00 AC: 0 AN: 44598

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26078

East Asian (EAS) AF: 0.00 AC: 0 AN: 39520

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 85954

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53316

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000632 AC: 7 AN: 1107142

Other (OTH) AF: 0.00 AC: 0 AN: 60166

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.7
DANN	Benign	0.73
PhyloP100		-0.13
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: rs1278502113; hg19: chr3-134264655;