NM_015147.3:c.427A>G

Variant names:

• chr2-65071523-A-G
• rs13389745
• NM_015147.3:c.427A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015147.3(CEP68):​c.427A>G​(p.Ile143Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,613,124 control chromosomes in the GnomAD database, including 1,594 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.058 (834 hom., cov: 32)
  • Exomes 𝑓: 0.0058 (760 hom.)
• Consequence: CEP68 NM_015147.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 7 publications found

Genes affected

CEP68 (HGNC:29076): (centrosomal protein 68) Enables protein domain specific binding activity and protein kinase binding activity. Involved in centriole-centriole cohesion and protein localization to organelle. Located in several cellular components, including centriolar satellite; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RAB1A (HGNC:9758): (RAB1A, member RAS oncogene family) This gene encodes a member of the Ras superfamily of GTPases. Members of the gene family cycle between inactive GDP-bound and active GTP-bound forms. This small GTPase controls vesicle traffic from the endoplasmic reticulum to the Golgi apparatus. Multiple alternatively spliced transcript variants have been identified for this gene which encode different protein isoforms. [provided by RefSeq, Oct 2008]

RAB1A Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0036167204).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP68	NM_015147.3	c.427A>G	p.Ile143Val	missense_variant	Exon 3 of 7	ENST00000377990.7	NP_055962.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP68	ENST00000377990.7	c.427A>G	p.Ile143Val	missense_variant	Exon 3 of 7	1	NM_015147.3	ENSP00000367229.2

Frequencies

GnomAD3 genomes AF: 0.0576 AC: 8726 AN: 151522 Hom.: 829 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0228

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000833

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000767

Gnomad OTH AF: 0.0480

GnomAD2 exomes AF: 0.0153 AC: 3835 AN: 251458 AF XY: 0.0113

Gnomad AFR exome AF: 0.210

Gnomad AMR exome AF: 0.00920

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000501

Gnomad OTH exome AF: 0.00668

GnomAD4 exome AF: 0.00584 AC: 8537 AN: 1461484 Hom.: 760 Cov.: 31 AF XY: 0.00511 AC XY: 3713 AN XY: 727060

African (AFR) AF: 0.202 AC: 6761 AN: 33472

American (AMR) AF: 0.0109 AC: 487 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000603 AC: 52 AN: 86246

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53414

Middle Eastern (MID) AF: 0.00815 AC: 47 AN: 5766

European-Non Finnish (NFE) AF: 0.000358 AC: 398 AN: 1111646

Other (OTH) AF: 0.0131 AC: 789 AN: 60384

GnomAD4 genome AF: 0.0578 AC: 8765 AN: 151640 Hom.: 834 Cov.: 32 AF XY: 0.0562 AC XY: 4169 AN XY: 74138

African (AFR) AF: 0.200 AC: 8261 AN: 41318

American (AMR) AF: 0.0228 AC: 347 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000625 AC: 3 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10540

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.000767 AC: 52 AN: 67822

Other (OTH) AF: 0.0475 AC: 100 AN: 2104

Alfa AF: 0.0215 Hom.: 575

Bravo AF: 0.0650

ESP6500AA AF: 0.194 AC: 853

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.0190 AC: 2301

Asia WGS AF: 0.0140 AC: 48 AN: 3478

EpiCase AF: 0.000654

EpiControl AF: 0.000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.011
DANN	Benign	0.54
DEOGEN2	Benign	0.0014	T;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.48	T;T
MetaRNN	Benign	0.0036	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.14	N;N
PhyloP100		-1.1
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.33	N;N
REVEL	Benign	0.044
Sift	Benign	0.80	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.013
MPC		0.040
ClinPred		0.0012	T
GERP RS		-0.64
Varity_R		0.044
gMVP		0.063
Mutation Taster		=300/0	polymorphism (auto)

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: rs13389745; hg19: chr2-65298657;