Genetic Variant CDIPT:p.Ala206Glu (chr16-29859214-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006319.5(CDIPT):c.617C>A(p.Ala206Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,445,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A206V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CDIPT
NM_006319.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.948

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09035674).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006319.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDIPT	NM_006319.5	MANE Select	c.617C>A	p.Ala206Glu	missense	Exon 6 of 6	NP_006310.1	O14735-1
CDIPT	NM_001286585.2		c.482C>A	p.Ala161Glu	missense	Exon 5 of 5	NP_001273514.1	O14735-3
CDIPT	NM_001286586.2		c.422C>A	p.Ala141Glu	missense	Exon 6 of 6	NP_001273515.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDIPT	ENST00000219789.11	TSL:1 MANE Select	c.617C>A	p.Ala206Glu	missense	Exon 6 of 6	ENSP00000219789.6	O14735-1
CDIPT	ENST00000934102.1		c.749C>A	p.Ala250Glu	missense	Exon 6 of 6	ENSP00000604161.1
CDIPT	ENST00000561555.5	TSL:2	c.689C>A	p.Ala230Glu	missense	Exon 4 of 4	ENSP00000455042.1	B3KY94

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.92e-7

AC:

AN:

1445108

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

717164

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33346

American (AMR)

AF:

0.00

AC:

AN:

41604

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25648

East Asian (EAS)

AF:

0.00

AC:

AN:

39162

South Asian (SAS)

AF:

0.00

AC:

AN:

83300

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51496

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

9.05e-7

AC:

AN:

1105072

Other (OTH)

AF:

0.00

AC:

AN:

59782

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.24

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.78

M_CAP

Benign

0.016

MetaRNN

Benign

0.090

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.6

PhyloP100

0.95

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.2

REVEL

Benign

0.071

Sift

Benign

0.17

Sift4G

Benign

0.12

Polyphen

0.079

Vest4

0.31

MutPred

0.49

Gain of solvent accessibility (P = 0.0145)

MVP

0.44

MPC

0.64

ClinPred

0.16

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.084

gMVP

0.72

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over