rs1673607

chr3-138570379-C-Achr3-138570379-C-Gchr3-138570379-C-T

Variant summary

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

The NM_024491.4(CEP70):c.404G>T(p.Ser135Ile) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S135N) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CEP70 NM_024491.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.194

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=0.25979504).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP70	NM_024491.4	c.404G>T	p.Ser135Ile	missense_variant	6/18	ENST00000264982.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP70	ENST00000264982.8	c.404G>T	p.Ser135Ile	missense_variant	6/18	1	NM_024491.4	A2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
Cadd	Benign	12
Dann	Benign	0.85
DEOGEN2	Benign	0.044	T;T;.;.;T;.;.
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.27	N
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.26	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;L;.;L;.;.;L
MutationTaster	Benign	1.0	P;P;P;P;P;P;P
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.5	D;D;N;N;D;D;D
REVEL	Benign	0.059
Sift	Benign	0.069	T;T;D;D;D;D;T
Sift4G	Benign	0.15	T;T;T;T;.;.;T
Polyphen		0.010	B;B;.;B;.;.;.
Vest4		0.14
MutPred		0.18		Loss of phosphorylation at S135 (P = 0.0343);Loss of phosphorylation at S135 (P = 0.0343);.;Loss of phosphorylation at S135 (P = 0.0343);.;.;Loss of phosphorylation at S135 (P = 0.0343);
MVP		0.38
MPC		0.051
ClinPred		0.16	T
GERP RS		-0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.098
gMVP		0.097

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: rs1673607; hg19: chr3-138289221;