16-4513040-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 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. 15/21 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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDIP1	NM_013399.3	c.266A>C	p.His89Pro	missense_variant	5/6	ENST00000567695.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDIP1	ENST00000567695.6	c.266A>C	p.His89Pro	missense_variant	5/6	1	NM_013399.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 27, 2022

The c.266A>C (p.H89P) alteration is located in exon 5 (coding exon 3) of the CDIP1 gene. This alteration results from a A to C substitution at nucleotide position 266, causing the histidine (H) at amino acid position 89 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T;T;.;.
Eigen	Benign	-0.14
Eigen_PC	Benign	0.089
FATHMM_MKL	Uncertain	0.90	D
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.20	T;T;T;T;T
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	1.2	L;L;L;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Benign	0.44	T
PROVEAN	Benign	0.27	N;N;N;D;.
Sift	Benign	0.33	T;T;T;D;.
Sift4G	Benign	0.22	T;T;T;.;T
Polyphen		0.0010	B;B;B;.;.
Vest4		0.41
MutPred		0.33		Gain of glycosylation at H89 (P = 0.0011);Gain of glycosylation at H89 (P = 0.0011);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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-4563041;