3-138500403-T-A

Position:

• chr3-138500403-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024491.4(CEP70):​c.1533A>T​(p.Glu511Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CEP70 NM_024491.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.600

Genes affected

CEP70 (HGNC:29972): (centrosomal protein 70) Enables identical protein binding activity. Predicted to be involved in cilium assembly and regulation of microtubule cytoskeleton organization. Located in centrosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12106201).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP70	NM_024491.4	c.1533A>T	p.Glu511Asp	missense_variant	15/18	ENST00000264982.8	NP_077817.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP70	ENST00000264982.8	c.1533A>T	p.Glu511Asp	missense_variant	15/18	1	NM_024491.4	ENSP00000264982.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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 03, 2022

The c.1533A>T (p.E511D) alteration is located in exon 15 (coding exon 13) of the CEP70 gene. This alteration results from a A to T substitution at nucleotide position 1533, causing the glutamic acid (E) at amino acid position 511 to be replaced by an aspartic acid (D). 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	Benign	0.11
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.016	T;.;T;.;.
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.38
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.65	.;T;T;T;T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.12	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;.;L;.;L
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.31	N;N;N;N;N
REVEL	Benign	0.013
Sift	Benign	0.41	T;T;T;T;T
Sift4G	Benign	0.37	T;T;T;T;T
Polyphen		0.0040	B;B;B;.;D
Vest4		0.15
MutPred		0.22		Loss of disorder (P = 0.1716);.;Loss of disorder (P = 0.1716);.;Loss of disorder (P = 0.1716);
MVP		0.43
MPC		0.24
ClinPred		0.39	T
GERP RS		2.5
Varity_R		0.042
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr3-138219245;