rs756182128

Variant names:

• chr11-117409800-A-C
• rs756182128
• NM_014956.5:c.3931A>C
• CEP164 p.Thr1311Pro

Your query was ambiguous. Multiple possible variants found:

• chr11-117409800-A-C
• chr11-117409800-A-G
• chr11-117409800-A-T

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.3931A>C​(p.Thr1311Pro) 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. T1311S) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.33 (0 hom., cov: 0)
  • Exomes 𝑓: 0.091 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CEP164 NM_014956.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.17
• Publications: 6 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, G2P
• 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=0.0033161342).
• BP6: Variant 11-117409800-A-C is Benign according to our data. Variant chr11-117409800-A-C is described in ClinVar as Benign. ClinVar VariationId is 706985.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.3931A>C	p.Thr1311Pro	missense	Exon 30 of 33	NP_055771.4
	CEP164	NM_001440949.1		c.3937A>C	p.Thr1313Pro	missense	Exon 30 of 33	NP_001427878.1
	CEP164	NM_001440950.1		c.3931A>C	p.Thr1311Pro	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.3931A>C	p.Thr1311Pro	missense	Exon 30 of 33	ENSP00000278935.3	Q9UPV0-1
	CEP164	ENST00000533223.1	TSL:1	n.4789A>C		non_coding_transcript_exon	Exon 16 of 16
	CEP164	ENST00000957770.1		c.3862A>C	p.Thr1288Pro	missense	Exon 27 of 30	ENSP00000627829.1

Frequencies

GnomAD3 genomes AF: 0.330 AC: 17947 AN: 54340 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.181

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.358

GnomAD2 exomes AF: 0.0664 AC: 12067 AN: 181822 AF XY: 0.0624

Gnomad AFR exome AF: 0.0474

Gnomad AMR exome AF: 0.103

Gnomad ASJ exome AF: 0.0851

Gnomad EAS exome AF: 0.0942

Gnomad FIN exome AF: 0.0386

Gnomad NFE exome AF: 0.0696

Gnomad OTH exome AF: 0.0944

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0910 AC: 41369 AN: 454522 Hom.: 0 Cov.: 35 AF XY: 0.0933 AC XY: 21743 AN XY: 232980

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0565 AC: 740 AN: 13090

American (AMR) AF: 0.0858 AC: 1884 AN: 21968

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 965 AN: 9588

East Asian (EAS) AF: 0.110 AC: 1124 AN: 10240

South Asian (SAS) AF: 0.144 AC: 5812 AN: 40240

European-Finnish (FIN) AF: 0.126 AC: 2968 AN: 23516

Middle Eastern (MID) AF: 0.0346 AC: 94 AN: 2720

European-Non Finnish (NFE) AF: 0.0822 AC: 25923 AN: 315380

Other (OTH) AF: 0.105 AC: 1859 AN: 17780

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.330 AC: 17948 AN: 54384 Hom.: 0 Cov.: 0 AF XY: 0.308 AC XY: 7978 AN XY: 25894

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.298 AC: 4429 AN: 14858

American (AMR) AF: 0.257 AC: 1201 AN: 4668

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 523 AN: 1302

East Asian (EAS) AF: 0.276 AC: 490 AN: 1774

South Asian (SAS) AF: 0.296 AC: 511 AN: 1728

European-Finnish (FIN) AF: 0.128 AC: 401 AN: 3142

Middle Eastern (MID) AF: 0.171 AC: 12 AN: 70

European-Non Finnish (NFE) AF: 0.387 AC: 9974 AN: 25744

Other (OTH) AF: 0.355 AC: 273 AN: 768

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.282 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.068
DANN	Benign	0.65
DEOGEN2	Benign	0.0060	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.20	T
MetaRNN	Benign	0.0033	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		-1.2
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.036
Sift	Benign	0.23	T
Sift4G	Benign	0.29	T
Varity_R		0.090
gMVP		0.15
Mutation Taster		=93/7	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs756182128;

hg19: chr11-117280516;

COSMIC: COSV54038338;

COSMIC: COSV54038338;