NM_014956.5:c.3932C>G

Variant names:

• chr11-117409801-C-G
• rs61743854
• NM_014956.5:c.3932C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_014956.5(CEP164):​c.3932C>G​(p.Thr1311Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T1311P) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.018 (93 hom., cov: 30)
  • Exomes 𝑓: 0.0019 (75 hom.)
  • Failed GnomAD Quality Control
• Consequence: CEP164 NM_014956.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.137
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0025037527).
• BP6: Variant 11-117409801-C-G is Benign according to our data. Variant chr11-117409801-C-G is described in ClinVar as Benign. ClinVar VariationId is 260488.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.3932C>G	p.Thr1311Ser	missense	Exon 30 of 33	NP_055771.4
	CEP164	NM_001440949.1		c.3938C>G	p.Thr1313Ser	missense	Exon 30 of 33	NP_001427878.1
	CEP164	NM_001440950.1		c.3932C>G	p.Thr1311Ser	missense	Exon 30 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.3932C>G	p.Thr1311Ser	missense	Exon 30 of 33	ENSP00000278935.3	Q9UPV0-1
	CEP164	ENST00000533223.1	TSL:1	n.4790C>G		non_coding_transcript_exon	Exon 16 of 16
	CEP164	ENST00000957770.1		c.3863C>G	p.Thr1288Ser	missense	Exon 27 of 30	ENSP00000627829.1

Frequencies

GnomAD3 genomes AF: 0.0178 AC: 2673 AN: 149860 Hom.: 93 Cov.: 30

Gnomad AFR AF: 0.0607

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0112

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000222

Gnomad OTH AF: 0.0157

GnomAD2 exomes AF: 0.00444 AC: 1115 AN: 250884 AF XY: 0.00316

Gnomad AFR exome AF: 0.0576

Gnomad AMR exome AF: 0.00379

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000247

Gnomad OTH exome AF: 0.00212

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00191 AC: 2789 AN: 1461106 Hom.: 75 Cov.: 79 AF XY: 0.00162 AC XY: 1180 AN XY: 726884

African (AFR) AF: 0.0640 AC: 2142 AN: 33474

American (AMR) AF: 0.00438 AC: 196 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26130

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

South Asian (SAS) AF: 0.000151 AC: 13 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52990

Middle Eastern (MID) AF: 0.00312 AC: 18 AN: 5768

European-Non Finnish (NFE) AF: 0.000110 AC: 122 AN: 1111702

Other (OTH) AF: 0.00490 AC: 296 AN: 60372

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0179 AC: 2680 AN: 149974 Hom.: 93 Cov.: 30 AF XY: 0.0172 AC XY: 1259 AN XY: 73134

African (AFR) AF: 0.0607 AC: 2463 AN: 40610

American (AMR) AF: 0.0112 AC: 169 AN: 15064

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5064

South Asian (SAS) AF: 0.00 AC: 0 AN: 4612

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10472

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000222 AC: 15 AN: 67424

Other (OTH) AF: 0.0155 AC: 32 AN: 2064

Alfa AF: 0.00215 Hom.: 2

Bravo AF: 0.0211

ESP6500AA AF: 0.0513 AC: 226

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00527 AC: 640

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Nephronophthisis 15 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.14
DANN	Benign	0.49
DEOGEN2	Benign	0.0070	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.21	T
MetaRNN	Benign	0.0025	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		-0.14
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.013
Sift	Benign	0.76	T
Sift4G	Benign	0.58	T
Polyphen		0.0070	B
Vest4		0.12
MutPred		0.073		Loss of catalytic residue at T1311 (P = 0.1496)
MVP		0.040
MPC		0.12
ClinPred		0.0027	T
GERP RS		-8.1
Varity_R		0.028
gMVP		0.13
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs61743854; hg19: chr11-117280517;