NM_014956.5:c.3001C>G

Variant names:

• chr11-117395634-C-G
• rs199637319
• NM_014956.5:c.3001C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_014956.5(CEP164):​c.3001C>G​(p.Leu1001Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000667 in 1,613,940 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.00044 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00069 (5 hom.)
• Consequence: CEP164 NM_014956.5 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:9
• Conservation: PhyloP100: 0.506
• Publications: 4 publications found

Genes affected

CEP164 (HGNC:29182): (centrosomal protein 164) This gene encodes a centrosomal protein involved in microtubule organization, DNA damage response, and chromosome segregation. The encoded protein is required for assembly of primary cilia and localizes to mature centrioles. Defects in this gene are a cause of nephronophthisis-related ciliopathies. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]

CEP164 Gene-Disease associations (from GenCC):

• CEP164-related ciliopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• nephronophthisis 15

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine
• Senior-Loken syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.022917122).
• BS2: High Homozygotes in GnomAdExome4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014956.5. 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
	CEP164	NM_014956.5	MANE Select	c.3001C>G	p.Leu1001Val	missense	Exon 24 of 33	NP_055771.4
	CEP164	NM_001440949.1		c.3010C>G	p.Leu1004Val	missense	Exon 24 of 33	NP_001427878.1
	CEP164	NM_001440950.1		c.3001C>G	p.Leu1001Val	missense	Exon 24 of 33	NP_001427879.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP164	ENST00000278935.8	TSL:1 MANE Select	c.3001C>G	p.Leu1001Val	missense	Exon 24 of 33	ENSP00000278935.3	Q9UPV0-1
	CEP164	ENST00000533223.1	TSL:1	n.3883C>G		non_coding_transcript_exon	Exon 10 of 16
	CEP164	ENST00000957770.1		c.2932C>G	p.Leu978Val	missense	Exon 21 of 30	ENSP00000627829.1

Frequencies

GnomAD3 genomes AF: 0.000434 AC: 66 AN: 152184 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000779

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000362 AC: 91 AN: 251216 AF XY: 0.000354

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000260

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000669

Gnomad OTH exome AF: 0.000816

GnomAD4 exome AF: 0.000691 AC: 1010 AN: 1461638 Hom.: 5 Cov.: 34 AF XY: 0.000641 AC XY: 466 AN XY: 727116

African (AFR) AF: 0.000179 AC: 6 AN: 33476

American (AMR) AF: 0.000402 AC: 18 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

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

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86232

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53388

Middle Eastern (MID) AF: 0.000715 AC: 4 AN: 5598

European-Non Finnish (NFE) AF: 0.000841 AC: 935 AN: 1112004

Other (OTH) AF: 0.000712 AC: 43 AN: 60382

GnomAD4 genome AF: 0.000440 AC: 67 AN: 152302 Hom.: 1 Cov.: 32 AF XY: 0.000457 AC XY: 34 AN XY: 74464

African (AFR) AF: 0.000144 AC: 6 AN: 41570

American (AMR) AF: 0.000327 AC: 5 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000779 AC: 53 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000754 Hom.: 0

Bravo AF: 0.000457

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000466 AC: 4

ExAC AF: 0.000231 AC: 28

EpiCase AF: 0.000981

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	3	-	Nephronophthisis 15 (3)
-	3	-	not provided (3)
-	1	-	CEP164-related disorder (1)
-	1	-	not specified (1)
-	1	-	Retinal dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	10
DANN	Benign	0.96
DEOGEN2	Benign	0.041	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.092	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.023	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.51
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.010
Sift	Benign	0.066	T
Sift4G	Benign	0.42	T
Polyphen		0.55	P
Vest4		0.073
MVP		0.14
MPC		0.20
ClinPred		0.036	T
GERP RS		0.29
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.033
gMVP		0.058
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: rs199637319; hg19: chr11-117266350;