rs1298398066

Variant names:

• chr1-91513246-C-G
• rs1298398066
• NM_003503.4:c.761C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-91513246-C-G
• chr1-91513246-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_003503.4(CDC7):​c.761C>G​(p.Ala254Gly) 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A254S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDC7 NM_003503.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.84
• Publications: 1 publications found

Genes affected

CDC7 (HGNC:1745): (cell division cycle 7) This gene encodes a cell division cycle protein with kinase activity that is critical for the G1/S transition. The yeast homolog is also essential for initiation of DNA replication as cell division occurs. Overexpression of this gene product may be associated with neoplastic transformation for some tumors. Multiple alternatively spliced transcript variants that encode the same protein have been detected. [provided by RefSeq, Aug 2008]

ENSG00000308368 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003503.4. 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
	CDC7	NM_003503.4	MANE Select	c.761C>G	p.Ala254Gly	missense	Exon 7 of 12	NP_003494.1	O00311-1
	CDC7	NM_001134419.2		c.761C>G	p.Ala254Gly	missense	Exon 7 of 12	NP_001127891.1	A0A384MTU6
	CDC7	NM_001134420.2		c.761C>G	p.Ala254Gly	missense	Exon 7 of 12	NP_001127892.1	A0A384MTU6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC7	ENST00000234626.11	TSL:1 MANE Select	c.761C>G	p.Ala254Gly	missense	Exon 7 of 12	ENSP00000234626.6	O00311-1
	CDC7	ENST00000428239.5	TSL:1	c.761C>G	p.Ala254Gly	missense	Exon 7 of 12	ENSP00000393139.1	O00311-1
	CDC7	ENST00000897932.1		c.761C>G	p.Ala254Gly	missense	Exon 7 of 12	ENSP00000567991.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.13
Eigen_PC	Benign	0.037
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.29	N
PhyloP100		4.8
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.024
Sift	Benign	0.075	T
Sift4G	Benign	0.38	T
Polyphen		0.22	B
Vest4		0.15
MutPred		0.31		Loss of glycosylation at T251 (P = 0.1119)
MVP		0.75
MPC		0.18
ClinPred		0.81	D
GERP RS		4.3
Varity_R		0.18
gMVP		0.19
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.66		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.66		Position offset: -1

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

Other links and lift over

dbSNP: rs1298398066; hg19: chr1-91978803;