NM_013399.3:c.191C>A

Variant names:

• chr16-4513746-G-T
• rs2058858161
• NM_013399.3:c.191C>A

Variant summary

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

The NM_013399.3(CDIP1):​c.191C>A​(p.Pro64His) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,390 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CDIP1 NM_013399.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.67
• 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.191C>A	p.Pro64His	missense	Exon 4 of 6	NP_037531.2	Q9H305-1
	CDIP1	NM_001199054.2		c.191C>A	p.Pro64His	missense	Exon 4 of 6	NP_001185983.1	Q9H305-1
	CDIP1	NM_001199055.2		c.191C>A	p.Pro64His	missense	Exon 4 of 6	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.191C>A	p.Pro64His	missense	Exon 4 of 6	ENSP00000457877.1	Q9H305-1
	CDIP1	ENST00000399599.7	TSL:1	c.191C>A	p.Pro64His	missense	Exon 3 of 5	ENSP00000382508.2	Q9H305-1
	CDIP1	ENST00000563332.6	TSL:1	c.191C>A	p.Pro64His	missense	Exon 4 of 6	ENSP00000454994.1	Q9H305-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461390 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727014

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111746

Other (OTH) AF: 0.00 AC: 0 AN: 60360

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	0.17
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.089	T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.84	T
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Uncertain	0.58	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		5.7
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.44
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.55
MutPred		0.26		Loss of relative solvent accessibility (P = 0.0404)
MVP		0.61
MPC		0.79
ClinPred		0.94	D
GERP RS		5.5
PromoterAI		0.032	Neutral
Varity_R		0.28
gMVP		0.41
Mutation Taster		=34/66	disease causing

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: rs2058858161; hg19: chr16-4563747;