chr3-101726605-A-C

Position:

• chr3-101726605-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024548.4(CEP97):​c.55A>C​(p.Asn19His) 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: 33)
• Consequence: CEP97 NM_024548.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.91

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP97	NM_024548.4	c.55A>C	p.Asn19His	missense_variant	2/11	ENST00000341893.8	NP_078824.2
CEP97	NM_001410784.1	c.55A>C	p.Asn19His	missense_variant	2/10		NP_001397713.1
CEP97	NM_001303401.2	c.55A>C	p.Asn19His	missense_variant	2/11		NP_001290330.1
CEP97	NM_001410785.1	c.55A>C	p.Asn19His	missense_variant	2/10		NP_001397714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP97	ENST00000341893.8	c.55A>C	p.Asn19His	missense_variant	2/11	1	NM_024548.4	ENSP00000342510.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 33

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

Feb 28, 2024

The c.55A>C (p.N19H) alteration is located in exon 2 (coding exon 2) of the CEP97 gene. This alteration results from a A to C substitution at nucleotide position 55, causing the asparagine (N) at amino acid position 19 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	Uncertain	0.46
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T;T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.60	D;D
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.5	L;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Benign	0.16
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.015	D;D
Polyphen		0.99	D;D
Vest4		0.59
MutPred		0.46		Loss of glycosylation at S21 (P = 0.0474);Loss of glycosylation at S21 (P = 0.0474);
MVP		0.69
MPC		0.59
ClinPred		0.97	D
GERP RS		3.6
Varity_R		0.52
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-101445449;