13-36437775-C-A

Variant names:

• chr13-36437775-C-A
• rs772143355
• NM_001413923.1:c.312C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001413923.1(CCNA1):​c.312C>A​(p.Asp104Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CCNA1 NM_001413923.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.262
• Publications: 0 publications found

Genes affected

CCNA1 (HGNC:1577): (cyclin A1) The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. The cyclin encoded by this gene was shown to be expressed in testis and brain, as well as in several leukemic cell lines, and is thought to primarily function in the control of the germline meiotic cell cycle. This cyclin binds both CDK2 and CDC2 kinases, which give two distinct kinase activities, one appearing in S phase, the other in G2, and thus regulate separate functions in cell cycle. This cyclin was found to bind to important cell cycle regulators, such as Rb family proteins, transcription factor E2F-1, and the p21 family proteins. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.065688014).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001413923.1. 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
	CCNA1	NM_001413923.1	MANE Select	c.312C>A	p.Asp104Glu	missense	Exon 3 of 9	NP_001400852.1	P78396-3
	CCNA1	NM_001111045.4		c.312C>A	p.Asp104Glu	missense	Exon 3 of 9	NP_001104515.2	P78396-3
	CCNA1	NM_001111046.2		c.312C>A	p.Asp104Glu	missense	Exon 3 of 9	NP_001104516.1	P78396-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNA1	ENST00000255465.8	TSL:1 MANE Select	c.312C>A	p.Asp104Glu	missense	Exon 3 of 9	ENSP00000255465.5	P78396-3
	CCNA1	ENST00000625767.2	TSL:1	c.312C>A	p.Asp104Glu	missense	Exon 3 of 9	ENSP00000486017.2	P78396-3
	CCNA1	ENST00000440264.5	TSL:2	c.312C>A	p.Asp104Glu	missense	Exon 3 of 9	ENSP00000400666.1	P78396-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461870 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727234

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111992

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.037
DANN	Benign	0.76
DEOGEN2	Benign	0.061	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.3	L
PhyloP100		-0.26
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.43	N
REVEL	Benign	0.0010
Sift	Benign	0.97	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.10
MutPred		0.25		Gain of disorder (P = 0.1621)
MVP		0.32
MPC		0.37
ClinPred		0.055	T
GERP RS		-1.1
Varity_R		0.031
gMVP		0.13
Mutation Taster		=94/6	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: rs772143355; hg19: chr13-37011912;