NM_013399.3:c.322C>A

Variant names:

• chr16-4512984-G-T
• rs773116696
• NM_013399.3:c.322C>A

Variant summary

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

The NM_013399.3(CDIP1):​c.322C>A​(p.Pro108Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,112 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P108S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CDIP1 NM_013399.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.33
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.322C>A	p.Pro108Thr	missense	Exon 5 of 6	NP_037531.2	Q9H305-1
	CDIP1	NM_001199054.2		c.322C>A	p.Pro108Thr	missense	Exon 5 of 6	NP_001185983.1	Q9H305-1
	CDIP1	NM_001199055.2		c.242-37C>A		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.322C>A	p.Pro108Thr	missense	Exon 5 of 6	ENSP00000457877.1	Q9H305-1
	CDIP1	ENST00000399599.7	TSL:1	c.322C>A	p.Pro108Thr	missense	Exon 4 of 5	ENSP00000382508.2	Q9H305-1
	CDIP1	ENST00000563332.6	TSL:1	c.322C>A	p.Pro108Thr	missense	Exon 5 of 6	ENSP00000454994.1	Q9H305-1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152112 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1437244 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 712490

African (AFR) AF: 0.00 AC: 0 AN: 33328

American (AMR) AF: 0.00 AC: 0 AN: 39686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25502

East Asian (EAS) AF: 0.00 AC: 0 AN: 38810

South Asian (SAS) AF: 0.00 AC: 0 AN: 82482

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50840

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1101386

Other (OTH) AF: 0.00 AC: 0 AN: 59498

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152112 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74310

African (AFR) AF: 0.0000483 AC: 2 AN: 41432

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67982

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

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	0.081
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.039	T
Eigen	Uncertain	0.58
Eigen_PC	Pathogenic	0.66
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Uncertain	0.18	D
MutationAssessor	Benign	1.7	L
PhyloP100		7.3
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.0	N
REVEL	Uncertain	0.40
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.33	T
Polyphen		0.98	D
Vest4		0.55
MVP		0.41
MPC		0.55
ClinPred		0.71	D
GERP RS		6.0
Varity_R		0.10
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs773116696; hg19: chr16-4562985;