16-29859520-C-T

Variant names:

• chr16-29859520-C-T
• rs745700199
• NM_006319.5:c.418G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006319.5(CDIPT):​c.418G>A​(p.Ala140Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,459,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CDIPT NM_006319.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.89

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37343377).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDIPT	NM_006319.5	c.418G>A	p.Ala140Thr	missense_variant	Exon 5 of 6	ENST00000219789.11	NP_006310.1
CDIPT	NM_001286585.2	c.283G>A	p.Ala95Thr	missense_variant	Exon 4 of 5		NP_001273514.1
CDIPT	NM_001286586.2	c.223G>A	p.Ala75Thr	missense_variant	Exon 5 of 6		NP_001273515.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDIPT	ENST00000219789.11	c.418G>A	p.Ala140Thr	missense_variant	Exon 5 of 6	1	NM_006319.5	ENSP00000219789.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248690 Hom.: 0 AF XY: 0.00000744 AC XY: 1 AN XY: 134462

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000465

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1459520 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 725984

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: 0.0000187

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;T;.;T;T
Eigen	Benign	-0.15
Eigen_PC	Benign	0.11
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	.;D;D;.;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.37	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.69	N;.;.;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.39	N;N;N;N;N
REVEL	Benign	0.10
Sift	Uncertain	0.0040	D;T;D;D;D
Sift4G	Uncertain	0.0080	D;D;T;D;D
Polyphen		0.049	B;B;.;B;B
Vest4		0.55
MutPred		0.51		.;Gain of sheet (P = 0.0344);.;.;.;
MVP		0.49
MPC		0.34
ClinPred		0.51	D
GERP RS		5.6
Varity_R		0.13
gMVP		0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs745700199; hg19: chr16-29870841;