rs1060499739

Positions:

• chr3-101757754-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2 PP5_Moderate BP4

The NM_024548.4(CEP97):​c.1148A>G​(p.His383Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CEP97 NM_024548.4 missense
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 3.71

Genes affected

CEP97 (HGNC:26244): (centrosomal protein 97) Predicted to enable calmodulin binding activity. Involved in negative regulation of cilium assembly and regulation of mitotic spindle assembly. Located in centriolar satellite and cytosol. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

CEP97 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 3-101757754-A-G is Pathogenic according to our data. Variant chr3-101757754-A-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 402141.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-101757754-A-G is described in Lovd as [Pathogenic].
• BP4: Computational evidence support a benign effect (MetaRNN=0.22271606). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP97	NM_024548.4	c.1148A>G	p.His383Arg	missense_variant	9/11	ENST00000341893.8	NP_078824.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP97	ENST00000341893.8	c.1148A>G	p.His383Arg	missense_variant	9/11	1	NM_024548.4	ENSP00000342510.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Global developmental delay;C3714756:Intellectual disability Pathogenic:1

Likely pathogenic, criteria provided, single submitter

research

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.067	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.076
Sift	Benign	0.052	T
Sift4G	Benign	0.22	T
Polyphen		0.0010	B
Vest4		0.48
MutPred		0.41		Gain of glycosylation at S378 (P = 0.0455);
MVP		0.57
MPC		0.17
ClinPred		0.59	D
GERP RS		3.9
Varity_R		0.14
gMVP		0.54

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: rs1060499739; hg19: chr3-101476598;