NM_015891.3:c.310A>T

Variant names:

• chr6-110201591-A-T
• NM_015891.3:c.310A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015891.3(CDC40):​c.310A>T​(p.Met104Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDC40 NM_015891.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.70
• Publications: 0 publications found

Genes affected

CDC40 (HGNC:17350): (cell division cycle 40) Pre-mRNA splicing occurs in two sequential transesterification steps. The protein encoded by this gene is found to be essential for the catalytic step II in pre-mRNA splicing process. It is found in the spliceosome, and contains seven WD repeats, which function in protein-protein interactions. This protein has a sequence similarity to yeast Prp17 protein, which functions in two different cellular processes: pre-mRNA splicing and cell cycle progression. It suggests that this protein may play a role in cell cycle progression. [provided by RefSeq, Jul 2008]

CDC40 Gene-Disease associations (from GenCC):

• pontocerebellar hypoplasia, type 15

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29684684).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015891.3. 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
	CDC40	NM_015891.3	MANE Select	c.310A>T	p.Met104Leu	missense	Exon 3 of 15	NP_056975.1	O60508

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC40	ENST00000307731.2	TSL:1 MANE Select	c.310A>T	p.Met104Leu	missense	Exon 3 of 15	ENSP00000304370.1	O60508
	CDC40	ENST00000924587.1		c.310A>T	p.Met104Leu	missense	Exon 3 of 15	ENSP00000594646.1
	CDC40	ENST00000368932.5	TSL:5	c.310A>T	p.Met104Leu	missense	Exon 4 of 16	ENSP00000357928.1	O60508

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

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	0.28
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.10	T
Eigen	Benign	0.038
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		8.7
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.19
Sift	Benign	0.39	T
Sift4G	Benign	0.33	T
Polyphen		0.0070	B
Vest4		0.56
MutPred		0.31		Gain of sheet (P = 0.0166)
MVP		0.70
MPC		0.73
ClinPred		0.80	D
GERP RS		5.7
Varity_R		0.61
gMVP		0.50
Mutation Taster		=55/45	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

hg19: chr6-110522794;