NM_013399.3:c.266A>C

Variant names:

• chr16-4513040-T-G
• NM_013399.3:c.266A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013399.3(CDIP1):​c.266A>C​(p.His89Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CDIP1 NM_013399.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.43
• Publications: 0 publications found

Genes affected

CDIP1 (HGNC:13234): (cell death inducing p53 target 1) Predicted to enable metal ion binding activity. Acts upstream of or within intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator and tumor necrosis factor-mediated signaling pathway. Located in cytoplasmic side of late endosome membrane; cytoplasmic side of lysosomal membrane; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19949707).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013399.3. 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
	CDIP1	NM_013399.3	MANE Select	c.266A>C	p.His89Pro	missense	Exon 5 of 6	NP_037531.2	Q9H305-1
	CDIP1	NM_001199054.2		c.266A>C	p.His89Pro	missense	Exon 5 of 6	NP_001185983.1	Q9H305-1
	CDIP1	NM_001199055.2		c.242-93A>C		intron	N/A	NP_001185984.1	Q9H305-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDIP1	ENST00000567695.6	TSL:1 MANE Select	c.266A>C	p.His89Pro	missense	Exon 5 of 6	ENSP00000457877.1	Q9H305-1
	CDIP1	ENST00000399599.7	TSL:1	c.266A>C	p.His89Pro	missense	Exon 4 of 5	ENSP00000382508.2	Q9H305-1
	CDIP1	ENST00000563332.6	TSL:1	c.266A>C	p.His89Pro	missense	Exon 5 of 6	ENSP00000454994.1	Q9H305-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

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	0.080
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.089
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	1.2	L
PhyloP100		3.4
PrimateAI	Benign	0.44	T
PROVEAN	Benign	0.27	N
REVEL	Benign	0.21
Sift	Benign	0.33	T
Sift4G	Benign	0.22	T
Polyphen		0.0010	B
Vest4		0.41
MutPred		0.33		Gain of glycosylation at H89 (P = 0.0011)
MVP		0.36
MPC		0.42
ClinPred		0.40	T
GERP RS		6.0
Varity_R		0.15
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr16-4563041;