1-243156259-G-A

Variant names:

• chr1-243156259-G-A
• rs183936101
• NM_014812.3:c.3873C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_014812.3(CEP170):​c.3873C>T​(p.Tyr1291Tyr) variant causes a synonymous change. The variant allele was found at a frequency of 0.00332 in 1,590,598 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0045 (8 hom., cov: 30)
  • Exomes 𝑓: 0.0032 (36 hom.)
• Consequence: CEP170 NM_014812.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 4.60
• Publications: 0 publications found

Genes affected

CEP170 (HGNC:28920): (centrosomal protein 170) The product of this gene is a component of the centrosome, a non-membraneous organelle that functions as the major microtubule-organizing center in animal cells. During interphase, the encoded protein localizes to the sub-distal appendages of mature centrioles, which are microtubule-based structures thought to help organize centrosomes. During mitosis, the protein associates with spindle microtubules near the centrosomes. The protein interacts with and is phosphorylated by polo-like kinase 1, and functions in maintaining microtubule organization and cell morphology. The human genome contains a putative transcribed pseudogene. Several alternatively spliced transcript variants of this gene have been found, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.168).
• BP6: Variant 1-243156259-G-A is Benign according to our data. Variant chr1-243156259-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 781679.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 681 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014812.3. 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
	CEP170	NM_014812.3	MANE Select	c.3873C>T	p.Tyr1291Tyr	synonymous	Exon 14 of 20	NP_055627.2	Q5SW79-1
	CEP170	NM_001042404.2		c.3579C>T	p.Tyr1193Tyr	synonymous	Exon 13 of 19	NP_001035863.1	Q5SW79-3
	CEP170	NM_001042405.2		c.3471C>T	p.Tyr1157Tyr	synonymous	Exon 13 of 19	NP_001035864.1	Q5SW79-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP170	ENST00000366542.6	TSL:5 MANE Select	c.3873C>T	p.Tyr1291Tyr	synonymous	Exon 14 of 20	ENSP00000355500.1	Q5SW79-1
	CEP170	ENST00000366544.6	TSL:5	c.3579C>T	p.Tyr1193Tyr	synonymous	Exon 13 of 19	ENSP00000355502.1	Q5SW79-3
	CEP170	ENST00000366543.5	TSL:5	c.3471C>T	p.Tyr1157Tyr	synonymous	Exon 13 of 19	ENSP00000355501.1	Q5SW79-2

Frequencies

GnomAD3 genomes AF: 0.00453 AC: 681 AN: 150192 Hom.: 8 Cov.: 30

Gnomad AFR AF: 0.000270

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00383

Gnomad ASJ AF: 0.00664

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000215

Gnomad FIN AF: 0.0399

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00257

Gnomad OTH AF: 0.00244

GnomAD2 exomes AF: 0.00541 AC: 1032 AN: 190768 AF XY: 0.00500

Gnomad AFR exome AF: 0.000265

Gnomad AMR exome AF: 0.00238

Gnomad ASJ exome AF: 0.0102

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0345

Gnomad NFE exome AF: 0.00258

Gnomad OTH exome AF: 0.00494

GnomAD4 exome AF: 0.00319 AC: 4596 AN: 1440288 Hom.: 36 Cov.: 31 AF XY: 0.00308 AC XY: 2202 AN XY: 714146

African (AFR) AF: 0.000242 AC: 8 AN: 33098

American (AMR) AF: 0.00205 AC: 84 AN: 40892

Ashkenazi Jewish (ASJ) AF: 0.00912 AC: 235 AN: 25762

East Asian (EAS) AF: 0.00 AC: 0 AN: 38972

South Asian (SAS) AF: 0.0000724 AC: 6 AN: 82908

European-Finnish (FIN) AF: 0.0298 AC: 1555 AN: 52128

Middle Eastern (MID) AF: 0.00243 AC: 14 AN: 5750

European-Non Finnish (NFE) AF: 0.00224 AC: 2465 AN: 1101062

Other (OTH) AF: 0.00383 AC: 229 AN: 59716

GnomAD4 genome AF: 0.00453 AC: 681 AN: 150310 Hom.: 8 Cov.: 30 AF XY: 0.00643 AC XY: 471 AN XY: 73222

African (AFR) AF: 0.000269 AC: 11 AN: 40868

American (AMR) AF: 0.00382 AC: 57 AN: 14914

Ashkenazi Jewish (ASJ) AF: 0.00664 AC: 23 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5116

South Asian (SAS) AF: 0.000215 AC: 1 AN: 4650

European-Finnish (FIN) AF: 0.0399 AC: 410 AN: 10276

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00257 AC: 174 AN: 67750

Other (OTH) AF: 0.00241 AC: 5 AN: 2072

Alfa AF: 0.00358 Hom.: 2

Bravo AF: 0.00173

Asia WGS AF: 0.000578 AC: 2 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	5.5
DANN	Benign	0.45
PhyloP100		4.6
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

Other links and lift over

dbSNP: rs183936101; hg19: chr1-243319561;