3-138505374-T-G

Position:

• chr3-138505374-T-G

Variant summary

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

The NM_024491.4(CEP70):​c.1142A>C​(p.Lys381Thr) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CEP70 NM_024491.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.08

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=0.10454321).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP70	NM_024491.4	c.1142A>C	p.Lys381Thr	missense_variant	13/18	ENST00000264982.8	NP_077817.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP70	ENST00000264982.8	c.1142A>C	p.Lys381Thr	missense_variant	13/18	1	NM_024491.4	ENSP00000264982.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Nov 26, 2024

The c.1142A>C (p.K381T) alteration is located in exon 13 (coding exon 11) of the CEP70 gene. This alteration results from a A to C substitution at nucleotide position 1142, causing the lysine (K) at amino acid position 381 to be replaced by a threonine (T). 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	-0.14	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	23
DANN	Benign	0.93
DEOGEN2	Benign	0.035	T;.;T;.;.
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.86	.;D;D;D;D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.10	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;.;M;.;M
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-2.1	N;D;N;N;N
REVEL	Benign	0.069
Sift	Benign	0.17	T;T;T;T;T
Sift4G	Benign	0.37	T;T;T;T;T
Polyphen		0.93	P;B;P;.;B
Vest4		0.21
MutPred		0.22		Loss of ubiquitination at K381 (P = 0.0134);.;Loss of ubiquitination at K381 (P = 0.0134);.;Loss of ubiquitination at K381 (P = 0.0134);
MVP		0.52
MPC		0.26
ClinPred		0.61	D
GERP RS		4.0
Varity_R		0.10
gMVP		0.40

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: chr3-138224216;