17-64519410-C-T

Variant names:

• chr17-64519410-C-T
• NM_138363.3:c.563C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_138363.3(CEP95):​c.563C>T​(p.Ala188Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CEP95 NM_138363.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.63
• Publications: 0 publications found

Genes affected

CEP95 (HGNC:25141): (centrosomal protein 95) Located in centrosome and spindle pole. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138363.3. 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
	CEP95	NM_138363.3	MANE Select	c.563C>T	p.Ala188Val	missense	Exon 6 of 20	NP_612372.1	Q96GE4-1
	CEP95	NM_001316990.2		c.71C>T	p.Ala24Val	missense	Exon 5 of 19	NP_001303919.1	Q96GE4-2
	CEP95	NR_133644.2		n.703C>T		non_coding_transcript_exon	Exon 6 of 20

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP95	ENST00000556440.7	TSL:1 MANE Select	c.563C>T	p.Ala188Val	missense	Exon 6 of 20	ENSP00000450461.2	Q96GE4-1
	CEP95	ENST00000553956.6	TSL:1	n.*282C>T		non_coding_transcript_exon	Exon 6 of 20	ENSP00000452317.2	H0YJW6
	CEP95	ENST00000553956.6	TSL:1	n.*282C>T		3_prime_UTR	Exon 6 of 20	ENSP00000452317.2	H0YJW6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	26
DANN	Benign	0.92
DEOGEN2	Benign	0.21	T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.068	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		5.6
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.25
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.013	D
Polyphen		1.0	D
Vest4		0.75
MutPred		0.64		Gain of sheet (P = 0.039)
MVP		0.86
MPC		0.19
ClinPred		0.73	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.25
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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

hg19: chr17-62515528;