dbSNP rs779675840: CDIPT:p.Arg138Thr (chr16-29860582-C-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_006319.5(CDIPT):c.413G>C(p.Arg138Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,450,568 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CDIPT
NM_006319.5 missense, splice_region

Scores

Splicing: ADA: 0.01059

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.75

Variant links:

Genes affected

CDIPT (HGNC:1769): (CDP-diacylglycerol--inositol 3-phosphatidyltransferase) Phosphatidylinositol breakdown products are ubiquitous second messengers that function downstream of many G protein-coupled receptors and tyrosine kinases regulating cell growth, calcium metabolism, and protein kinase C activity. Two enzymes, CDP-diacylglycerol synthase and phosphatidylinositol synthase, are involved in the biosynthesis of phosphatidylinositol. Phosphatidylinositol synthase, a member of the CDP-alcohol phosphatidyl transferase class-I family, is an integral membrane protein found on the cytoplasmic side of the endoplasmic reticulum and the Golgi apparatus. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]

CDIPT links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.826

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDIPT	NM_006319.5 link	c.413G>C	p.Arg138Thr	missense_variant, splice_region_variant	Exon 4 of 6	ENST00000219789.11	NP_006310.1	O14735-1A8K3L7
CDIPT	NM_001286585.2 link	c.278G>C	p.Arg93Thr	missense_variant, splice_region_variant	Exon 3 of 5		NP_001273514.1	O14735-3A8K3L7
CDIPT	NM_001286586.2 link	c.218G>C	p.Arg73Thr	missense_variant, splice_region_variant	Exon 4 of 6		NP_001273515.1	A8K3L7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDIPT	ENST00000219789.11 link	c.413G>C	p.Arg138Thr	missense_variant, splice_region_variant	Exon 4 of 6	1	NM_006319.5	ENSP00000219789.6		O14735-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1450568

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722338

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000181

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.83

BayesDel_addAF

Uncertain

0.081

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.63

D;T;.;D;D;T

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.97

.;D;D;.;D;D

M_CAP

Benign

0.045

MetaRNN

Pathogenic

0.83

D;D;D;D;D;D

MetaSVM

Benign

-0.64

MutationAssessor

Uncertain

2.7

M;.;.;M;M;.

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-4.8

D;D;D;D;D;D

REVEL

Uncertain

0.33

Sift

Uncertain

0.0020

D;D;D;D;D;D

Sift4G

Uncertain

0.0040

D;D;D;D;D;D

Polyphen

0.99

D;D;.;D;D;.

Vest4

0.75

MutPred

0.56

.;Gain of sheet (P = 0.1208);.;.;.;.;

MVP

0.76

MPC

0.95

ClinPred

0.99

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.62

gMVP

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.011

dbscSNV1_RF

Benign

0.14

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over