11-117409801-C-A

Position:

• chr11-117409801-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014956.5(CEP164):​c.3932C>A​(p.Thr1311Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000667 in 149,870 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T1311S) has been classified as Benign.

• Frequency: Genomes: 𝑓 0.0000067 (0 hom., cov: 30)
• Consequence: CEP164 NM_014956.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.137

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054331094).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP164	NM_014956.5	c.3932C>A	p.Thr1311Asn	missense_variant	30/33	ENST00000278935.8	NP_055771.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP164	ENST00000278935.8	c.3932C>A	p.Thr1311Asn	missense_variant	30/33	1	NM_014956.5	ENSP00000278935.3

Frequencies

GnomAD3 genomes AF: 0.00000667 AC: 1 AN: 149870 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000247

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 79

GnomAD4 genome AF: 0.00000667 AC: 1 AN: 149870 Hom.: 0 Cov.: 30 AF XY: 0.0000137 AC XY: 1 AN XY: 73016

Gnomad4 AFR AF: 0.0000247

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.48
DANN	Benign	0.66
DEOGEN2	Benign	0.0088	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.039
Sift	Benign	0.32	T
Sift4G	Benign	0.42	T
Polyphen		0.22	B
Vest4		0.19
MutPred		0.11		Loss of glycosylation at T1311 (P = 0.0034);
MVP		0.030
MPC		0.26
ClinPred		0.33	T
GERP RS		-8.1
Varity_R		0.032
gMVP		0.15

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

Publications

LitVar

Other links and lift over

dbSNP: rs61743854; hg19: chr11-117280517;