3-138498063-T-C

Variant names:

• chr3-138498063-T-C
• rs2108652083
• NM_024491.4:c.1700A>G

Variant summary

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

The NM_024491.4(CEP70):​c.1700A>G​(p.Gln567Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CEP70 NM_024491.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.27
• Publications: 0 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 2 ACMG points.

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP70	NM_024491.4	MANE Select	c.1700A>G	p.Gln567Arg	missense	Exon 17 of 18	NP_077817.2	Q8NHQ1-1
	CEP70	NM_001320599.2		c.1700A>G	p.Gln567Arg	missense	Exon 17 of 18	NP_001307528.1
	CEP70	NM_001320598.2		c.1700A>G	p.Gln567Arg	missense	Exon 17 of 18	NP_001307527.1	A0A140VJG2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP70	ENST00000264982.8	TSL:1 MANE Select	c.1700A>G	p.Gln567Arg	missense	Exon 17 of 18	ENSP00000264982.3	Q8NHQ1-1
	CEP70	ENST00000882531.1		c.1760A>G	p.Gln587Arg	missense	Exon 18 of 19	ENSP00000552590.1
	CEP70	ENST00000484888.5	TSL:5	c.1700A>G	p.Gln567Arg	missense	Exon 17 of 18	ENSP00000419231.1	Q8NHQ1-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.091	T
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		4.3
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.13
Sift	Benign	0.12	T
Sift4G	Benign	0.51	T
Polyphen		0.99	D
Vest4		0.43
MutPred		0.40		Loss of helix (P = 0.0237)
MVP		0.48
MPC		0.31
ClinPred		0.94	D
GERP RS		2.8
Varity_R		0.075
gMVP		0.40
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.28		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.28		Position offset: 47

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

Other links and lift over

dbSNP: rs2108652083; hg19: chr3-138216905;