17-64510258-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_138363.3(CEP95):c.234G>T(p.Gln78His) variant causes a missense change. The variant allele was found at a frequency of 0.00000619 in 1,455,090 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (1 hom.)
• Consequence: CEP95 NM_138363.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.96

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.82

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP95	NM_138363.3	c.234G>T	p.Gln78His	missense_variant	3/20	ENST00000556440.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP95	ENST00000556440.7	c.234G>T	p.Gln78His	missense_variant	3/20	1	NM_138363.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000205 AC: 5 AN: 243932 Hom.: 1 AF XY: 0.0000227 AC XY: 3 AN XY: 132194

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000169

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000619 AC: 9 AN: 1455090 Hom.: 1 Cov.: 29 AF XY: 0.00000829 AC XY: 6 AN XY: 723870

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000105

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000508 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000248 AC: 3

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 17, 2024

The c.234G>T (p.Q78H) alteration is located in exon 3 (coding exon 3) of the CEP95 gene. This alteration results from a G to T substitution at nucleotide position 234, causing the glutamine (Q) at amino acid position 78 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Uncertain	0.059	T
BayesDel_noAF	Uncertain	0.11
Cadd	Benign	23
Dann	Uncertain	0.99
DEOGEN2	Benign	0.097	T;.;T
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Pathogenic	0.43	D
MetaRNN	Pathogenic	0.82	D;D;D
MetaSVM	Pathogenic	0.93	D
MutationAssessor	Uncertain	2.6	M;.;.
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-2.0	N;.;.
REVEL	Uncertain	0.58
Sift	Benign	0.059	T;.;.
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.80
MutPred		0.67		Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);
MVP		0.86
MPC		0.19
ClinPred		0.31	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs200297929; hg19: chr17-62506376;