NM_001253.4:c.279G>A

Variant names:

• chr6-44392796-G-A
• rs10948136
• NM_001253.4:c.279G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_001253.4(CDC5L):​c.279G>A​(p.Ala93Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0362 in 1,613,848 control chromosomes in the GnomAD database, including 2,171 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.049 (354 hom., cov: 33)
  • Exomes 𝑓: 0.035 (1817 hom.)
• Consequence: CDC5L NM_001253.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.251
• Publications: 8 publications found

Genes affected

CDC5L (HGNC:1743): (cell division cycle 5 like) The protein encoded by this gene shares a significant similarity with Schizosaccharomyces pombe cdc5 gene product, which is a cell cycle regulator important for G2/M transition. This protein has been demonstrated to act as a positive regulator of cell cycle G2/M progression. It was also found to be an essential component of a non-snRNA spliceosome, which contains at least five additional protein factors and is required for the second catalytic step of pre-mRNA splicing. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 6-44392796-G-A is Benign according to our data. Variant chr6-44392796-G-A is described in ClinVar as Benign. ClinVar VariationId is 1282740.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.251 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001253.4. 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
	CDC5L	NM_001253.4	MANE Select	c.279G>A	p.Ala93Ala	synonymous	Exon 3 of 16	NP_001244.1	Q99459

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC5L	ENST00000371477.4	TSL:1 MANE Select	c.279G>A	p.Ala93Ala	synonymous	Exon 3 of 16	ENSP00000360532.3	Q99459
	CDC5L	ENST00000862195.1		c.279G>A	p.Ala93Ala	synonymous	Exon 3 of 15	ENSP00000532254.1
	CDC5L	ENST00000918589.1		c.279G>A	p.Ala93Ala	synonymous	Exon 3 of 16	ENSP00000588648.1

Frequencies

GnomAD3 genomes AF: 0.0487 AC: 7414 AN: 152102 Hom.: 348 Cov.: 33

Gnomad AFR AF: 0.0316

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.0929

Gnomad SAS AF: 0.0493

Gnomad FIN AF: 0.0970

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0245

Gnomad OTH AF: 0.0544

GnomAD2 exomes AF: 0.0620 AC: 15580 AN: 251406 AF XY: 0.0575

Gnomad AFR exome AF: 0.0320

Gnomad AMR exome AF: 0.191

Gnomad ASJ exome AF: 0.0170

Gnomad EAS exome AF: 0.0913

Gnomad FIN exome AF: 0.0906

Gnomad NFE exome AF: 0.0245

Gnomad OTH exome AF: 0.0525

GnomAD4 exome AF: 0.0349 AC: 51028 AN: 1461628 Hom.: 1817 Cov.: 31 AF XY: 0.0350 AC XY: 25478 AN XY: 727120

African (AFR) AF: 0.0327 AC: 1094 AN: 33472

American (AMR) AF: 0.185 AC: 8272 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0163 AC: 427 AN: 26130

East Asian (EAS) AF: 0.103 AC: 4068 AN: 39680

South Asian (SAS) AF: 0.0512 AC: 4415 AN: 86246

European-Finnish (FIN) AF: 0.0846 AC: 4520 AN: 53402

Middle Eastern (MID) AF: 0.0421 AC: 243 AN: 5768

European-Non Finnish (NFE) AF: 0.0232 AC: 25816 AN: 1111824

Other (OTH) AF: 0.0360 AC: 2173 AN: 60388

GnomAD4 genome AF: 0.0488 AC: 7433 AN: 152220 Hom.: 354 Cov.: 33 AF XY: 0.0554 AC XY: 4122 AN XY: 74426

African (AFR) AF: 0.0315 AC: 1310 AN: 41542

American (AMR) AF: 0.165 AC: 2530 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0161 AC: 56 AN: 3472

East Asian (EAS) AF: 0.0927 AC: 481 AN: 5186

South Asian (SAS) AF: 0.0495 AC: 239 AN: 4828

European-Finnish (FIN) AF: 0.0970 AC: 1025 AN: 10566

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0245 AC: 1668 AN: 68008

Other (OTH) AF: 0.0539 AC: 114 AN: 2116

Alfa AF: 0.0365 Hom.: 258

Bravo AF: 0.0538

Asia WGS AF: 0.0690 AC: 239 AN: 3478

EpiCase AF: 0.0266

EpiControl AF: 0.0307

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	6.8
DANN	Benign	0.61
PhyloP100		0.25
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs10948136; hg19: chr6-44360533; COSMIC: COSV65177372;