11-65079672-G-A

Variant names:

• chr11-65079672-G-A
• rs760541197
• NM_080668.4:c.359C>T

Variant summary

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

The NM_080668.4(CDCA5):​c.359C>T​(p.Pro120Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,449,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. P120R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CDCA5 NM_080668.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 0 publications found

Genes affected

CDCA5 (HGNC:14626): (cell division cycle associated 5) Predicted to enable chromatin binding activity. Involved in double-strand break repair; mitotic sister chromatid segregation; and regulation of cell cycle process. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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=0.058347315).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080668.4. 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
	CDCA5	NM_080668.4	MANE Select	c.359C>T	p.Pro120Leu	missense	Exon 5 of 6	NP_542399.1	Q96FF9
	CDCA5	NM_001433518.1		c.359C>T	p.Pro120Leu	missense	Exon 5 of 10	NP_001420447.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDCA5	ENST00000275517.8	TSL:1 MANE Select	c.359C>T	p.Pro120Leu	missense	Exon 5 of 6	ENSP00000275517.3	Q96FF9
	CDCA5	ENST00000479032.6	TSL:1	n.629C>T		non_coding_transcript_exon	Exon 4 of 5
	CDCA5	ENST00000404147.3	TSL:2	c.359C>T	p.Pro120Leu	missense	Exon 5 of 5	ENSP00000385711.3	B5MBX0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000857 AC: 2 AN: 233350 AF XY: 0.0000158

Gnomad AFR exome AF: 0.000135

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1449148 Hom.: 0 Cov.: 32 AF XY: 0.00000417 AC XY: 3 AN XY: 719592

African (AFR) AF: 0.0000909 AC: 3 AN: 33020

American (AMR) AF: 0.00 AC: 0 AN: 43108

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25632

East Asian (EAS) AF: 0.00 AC: 0 AN: 39312

South Asian (SAS) AF: 0.00 AC: 0 AN: 84902

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52944

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5730

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1104730

Other (OTH) AF: 0.00 AC: 0 AN: 59770

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000330 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.037
DANN	Benign	0.63
DEOGEN2	Benign	0.015	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.81	N
PhyloP100		-1.2
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.064
Sift	Benign	0.35	T
Sift4G	Benign	0.54	T
Polyphen		0.0	B
Vest4		0.13
MVP		0.33
MPC		0.54
ClinPred		0.030	T
GERP RS		-6.6
PromoterAI		-0.0079	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.025
gMVP		0.11
Mutation Taster		=98/2	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: rs760541197; hg19: chr11-64847144;