rs1060499739

Variant names:

• chr3-101757754-A-G
• rs1060499739
• NM_024548.4:c.1148A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-101757754-A-G
• chr3-101757754-A-C

Variant summary

Our verdict is Uncertain significance. The variant received 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. 14/22 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
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 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 VariationId is 402141.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.22271606). . Strength limited to SUPPORTING due to the PP5.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024548.4. 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
	CEP97	NM_024548.4	MANE Select	c.1148A>G	p.His383Arg	missense	Exon 9 of 11	NP_078824.2
	CEP97	NM_001410784.1		c.1046A>G	p.His349Arg	missense	Exon 8 of 10	NP_001397713.1	A0A994J4L0
	CEP97	NM_001303401.2		c.1028-57A>G		intron	N/A	NP_001290330.1	E9PG22

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP97	ENST00000341893.8	TSL:1 MANE Select	c.1148A>G	p.His383Arg	missense	Exon 9 of 11	ENSP00000342510.3	Q8IW35-1
	CEP97	ENST00000489172.5	TSL:1	n.1130A>G		non_coding_transcript_exon	Exon 8 of 8
	CEP97	ENST00000704370.1		c.1142A>G	p.His381Arg	missense	Exon 9 of 11	ENSP00000515877.1	A0A994J704

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Global developmental delay;C3714756:Intellectual disability (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		3.7
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
Mutation Taster		=81/19	disease causing (ClinVar)

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: rs1060499739; hg19: chr3-101476598;