rs78544176

Variant names:

• chr11-93724366-C-G
• rs78544176
• NM_033395.2:c.6309C>G

Variant summary

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

The NM_033395.2(CEP295):​c.6309C>G​(p.Asp2103Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.06 in 1,546,140 control chromosomes in the GnomAD database, including 3,300 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.046 (242 hom., cov: 33)
  • Exomes 𝑓: 0.062 (3058 hom.)
• Consequence: CEP295 NM_033395.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0950
• Publications: 10 publications found

Genes affected

CEP295 (HGNC:29366): (centrosomal protein 295) Enables microtubule binding activity. Involved in several processes, including centriole replication; positive regulation of protein acetylation; and regulation of centrosome duplication. Located in cytosol; microtubule cytoskeleton; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0021867156).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP295	NM_033395.2	c.6309C>G	p.Asp2103Glu	missense_variant	Exon 22 of 30	ENST00000325212.11	NP_203753.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP295	ENST00000325212.11	c.6309C>G	p.Asp2103Glu	missense_variant	Exon 22 of 30	2	NM_033395.2	ENSP00000316681.6
CEP295	ENST00000531700.5	c.849C>G	p.Asp283Glu	missense_variant	Exon 9 of 17	2		ENSP00000437323.1
CEP295	ENST00000531404.1	c.345C>G	p.Asp115Glu	missense_variant	Exon 2 of 9	2		ENSP00000433650.1
CEP295	ENST00000529185.1	c.-94C>G		5_prime_UTR_variant	Exon 1 of 3	3		ENSP00000433198.1

Frequencies

GnomAD3 genomes AF: 0.0464 AC: 7054 AN: 152156 Hom.: 242 Cov.: 33

Gnomad AFR AF: 0.0126

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0374

Gnomad ASJ AF: 0.0179

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00870

Gnomad FIN AF: 0.0586

Gnomad MID AF: 0.0255

Gnomad NFE AF: 0.0742

Gnomad OTH AF: 0.0411

GnomAD2 exomes AF: 0.0417 AC: 6488 AN: 155546 AF XY: 0.0406

Gnomad AFR exome AF: 0.0106

Gnomad AMR exome AF: 0.0250

Gnomad ASJ exome AF: 0.0226

Gnomad EAS exome AF: 0.0000919

Gnomad FIN exome AF: 0.0571

Gnomad NFE exome AF: 0.0688

Gnomad OTH exome AF: 0.0445

GnomAD4 exome AF: 0.0615 AC: 85733 AN: 1393866 Hom.: 3058 Cov.: 30 AF XY: 0.0605 AC XY: 41571 AN XY: 687678

African (AFR) AF: 0.00888 AC: 280 AN: 31530

American (AMR) AF: 0.0265 AC: 939 AN: 35472

Ashkenazi Jewish (ASJ) AF: 0.0219 AC: 550 AN: 25160

East Asian (EAS) AF: 0.0000560 AC: 2 AN: 35706

South Asian (SAS) AF: 0.0133 AC: 1048 AN: 78890

European-Finnish (FIN) AF: 0.0598 AC: 2943 AN: 49232

Middle Eastern (MID) AF: 0.0237 AC: 135 AN: 5688

European-Non Finnish (NFE) AF: 0.0715 AC: 76777 AN: 1074334

Other (OTH) AF: 0.0529 AC: 3059 AN: 57854

GnomAD4 genome AF: 0.0463 AC: 7054 AN: 152274 Hom.: 242 Cov.: 33 AF XY: 0.0452 AC XY: 3369 AN XY: 74466

African (AFR) AF: 0.0125 AC: 521 AN: 41562

American (AMR) AF: 0.0372 AC: 569 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0179 AC: 62 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5188

South Asian (SAS) AF: 0.00892 AC: 43 AN: 4822

European-Finnish (FIN) AF: 0.0586 AC: 621 AN: 10600

Middle Eastern (MID) AF: 0.0274 AC: 8 AN: 292

European-Non Finnish (NFE) AF: 0.0742 AC: 5046 AN: 68010

Other (OTH) AF: 0.0407 AC: 86 AN: 2114

Alfa AF: 0.0629 Hom.: 256

Bravo AF: 0.0437

TwinsUK AF: 0.0761 AC: 282

ALSPAC AF: 0.0791 AC: 305

ESP6500AA AF: 0.0166 AC: 23

ESP6500EA AF: 0.0685 AC: 218

ExAC AF: 0.0325 AC: 780

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.020	T;.;T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.74	T;T;T
MetaRNN	Benign	0.0022	T;T;T
MetaSVM	Benign	-1.0	T
PhyloP100		0.095
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.6	N;N;D
REVEL	Benign	0.060
Sift	Benign	0.12	T;T;T
Sift4G	Benign	0.34	T;T;T
Polyphen		0.87	P;P;.
Vest4		0.16
MutPred		0.16		Gain of helix (P = 0.0854);.;.;
MPC		0.31
ClinPred		0.019	T
GERP RS		3.5
Varity_R		0.099
gMVP		0.035
Mutation Taster		=98/2	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: rs78544176; hg19: chr11-93457532; COSMIC: COSV108141556; COSMIC: COSV108141556;