NM_006319.5:c.436G>T

Variant names:

• chr16-29859502-C-A
• NM_006319.5:c.436G>T

Variant summary

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

The NM_006319.5(CDIPT):​c.436G>T​(p.Ala146Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDIPT NM_006319.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.65

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=0.33328283).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDIPT	NM_006319.5	c.436G>T	p.Ala146Ser	missense_variant	Exon 5 of 6	ENST00000219789.11	NP_006310.1
CDIPT	NM_001286585.2	c.301G>T	p.Ala101Ser	missense_variant	Exon 4 of 5		NP_001273514.1
CDIPT	NM_001286586.2	c.241G>T	p.Ala81Ser	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.436G>T	p.Ala146Ser	missense_variant	Exon 5 of 6	1	NM_006319.5	ENSP00000219789.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 01, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.436G>T (p.A146S) alteration is located in exon 5 (coding exon 5) of the CDIPT gene. This alteration results from a G to T substitution at nucleotide position 436, causing the alanine (A) at amino acid position 146 to be replaced by a serine (S). 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	0.32
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.37	T;T;.;T;T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	.;D;D;.;D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.33	T;T;T;T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.7	M;.;.;M;M
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.9	N;N;N;N;N
REVEL	Benign	0.097
Sift	Benign	0.049	D;T;T;D;D
Sift4G	Benign	0.22	T;T;T;T;T
Polyphen		0.29	B;B;.;B;B
Vest4		0.48
MutPred		0.47		.;Gain of sheet (P = 0.0477);.;.;.;
MVP		0.58
MPC		0.35
ClinPred		0.94	D
GERP RS		5.6
Varity_R		0.21
gMVP		0.50

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-29870823; COSMIC: COSV54888878; COSMIC: COSV54888878;