chr3-138570379-C-G

Variant names:

• chr3-138570379-C-G
• rs1673607
• NM_024491.4:c.404G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024491.4(CEP70):​c.404G>C​(p.Ser135Thr) 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. 16/22 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: 31)
• Consequence: CEP70 NM_024491.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.194
• Publications: 40 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2176654).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024491.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP70	NM_024491.4	MANE Select	c.404G>C	p.Ser135Thr	missense	Exon 6 of 18	NP_077817.2
	CEP70	NM_001320599.2		c.404G>C	p.Ser135Thr	missense	Exon 6 of 18	NP_001307528.1
	CEP70	NM_001320598.2		c.404G>C	p.Ser135Thr	missense	Exon 6 of 18	NP_001307527.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP70	ENST00000264982.8	TSL:1 MANE Select	c.404G>C	p.Ser135Thr	missense	Exon 6 of 18	ENSP00000264982.3
	CEP70	ENST00000481834.5	TSL:1	c.404G>C	p.Ser135Thr	missense	Exon 6 of 16	ENSP00000417465.1
	CEP70	ENST00000464035.5	TSL:1	c.404G>C	p.Ser135Thr	missense	Exon 5 of 6	ENSP00000419743.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	8.8
DANN	Benign	0.61
DEOGEN2	Benign	0.027	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.19
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.051
Sift	Benign	0.28	T
Sift4G	Benign	0.47	T
Polyphen		0.0040	B
Vest4		0.061
MutPred		0.097		Loss of phosphorylation at S135 (P = 0.0952)
MVP		0.34
MPC		0.044
ClinPred		0.10	T
GERP RS		-0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.047
gMVP		0.039
Mutation Taster		=97/3	polymorphism

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: rs1673607; hg19: chr3-138289221;