16-4512613-T-G

Variant names:

• chr16-4512613-T-G
• NM_013399.3:c.586A>C
• CDIP1 p.Ser196Arg

Variant summary

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

The NM_013399.3(CDIP1):​c.586A>C​(p.Ser196Arg) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDIP1 NM_013399.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.98
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.188).

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.586A>C	p.Ser196Arg	missense	Exon 6 of 6	NP_037531.2	Q9H305-1
	CDIP1	NM_001199054.2		c.586A>C	p.Ser196Arg	missense	Exon 6 of 6	NP_001185983.1	Q9H305-1
	CDIP1	NM_001199055.2		c.469A>C	p.Ser157Arg	missense	Exon 6 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.586A>C	p.Ser196Arg	missense	Exon 6 of 6	ENSP00000457877.1	Q9H305-1
	CDIP1	ENST00000399599.7	TSL:1	c.586A>C	p.Ser196Arg	missense	Exon 5 of 5	ENSP00000382508.2	Q9H305-1
	CDIP1	ENST00000563332.6	TSL:1	c.586A>C	p.Ser196Arg	missense	Exon 6 of 6	ENSP00000454994.1	Q9H305-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	26
DANN	Uncertain	0.98
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.019
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.059	D
PhyloP100		3.0
Varity_R		0.49

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-4562614;