20-35462397-C-T

Variant names:

• chr20-35462397-C-T
• rs747946549
• NM_007186.6:c.30C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_007186.6(CEP250):​c.30C>T​(p.Asn10Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,442,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CEP250 NM_007186.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.54
• Publications: 0 publications found

Genes affected

CEP250 (HGNC:1859): (centrosomal protein 250) This gene encodes a core centrosomal protein required for centriole-centriole cohesion during interphase of the cell cycle. The encoded protein dissociates from the centrosomes when parental centrioles separate at the beginning of mitosis. The protein associates with and is phosphorylated by NIMA-related kinase 2, which is also associated with the centrosome. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

CEP250 Gene-Disease associations (from GenCC):

• cone-rod dystrophy and hearing loss 2

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• retinitis pigmentosa

  Inheritance: AR Classification: LIMITED Submitted by: Franklin by Genoox
• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: NO_KNOWN Submitted by: King Faisal Specialist Hospital and Research Center

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 20-35462397-C-T is Benign according to our data. Variant chr20-35462397-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2789664.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.54 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007186.6. 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
	CEP250	NM_007186.6	MANE Select	c.30C>T	p.Asn10Asn	synonymous	Exon 4 of 35	NP_009117.2
	CEP250	NM_001318219.1		c.-1870C>T		5_prime_UTR	Exon 2 of 33	NP_001305148.1	Q9BV73

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP250	ENST00000397527.6	TSL:5 MANE Select	c.30C>T	p.Asn10Asn	synonymous	Exon 4 of 35	ENSP00000380661.1	Q9BV73-1
	CEP250	ENST00000446710.5	TSL:1	c.30C>T	p.Asn10Asn	synonymous	Exon 4 of 7	ENSP00000398747.1	Q5JWS5
	CEP250	ENST00000706828.1		c.30C>T	p.Asn10Asn	synonymous	Exon 4 of 36	ENSP00000516576.1	A0A9L9PXX3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1442408 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 715530

African (AFR) AF: 0.00 AC: 0 AN: 33058

American (AMR) AF: 0.00 AC: 0 AN: 41796

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25706

East Asian (EAS) AF: 0.00 AC: 0 AN: 38908

South Asian (SAS) AF: 0.00 AC: 0 AN: 83240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52128

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 9.07e-7 AC: 1 AN: 1102174

Other (OTH) AF: 0.00 AC: 0 AN: 59670

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	7.6
DANN	Benign	0.77
PhyloP100		1.5
PromoterAI		-0.030	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs747946549; hg19: chr20-34050222;