NM_020244.3:c.629C>A

Variant names:

• chr12-101716793-C-A
• rs369936908
• NM_020244.3:c.629C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020244.3(CHPT1):​c.629C>A​(p.Ala210Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,451,498 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 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: 33)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: CHPT1 NM_020244.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.68

Genes affected

CHPT1 (HGNC:17852): (choline phosphotransferase 1) Enables diacylglycerol cholinephosphotransferase activity. Involved in phosphatidylcholine biosynthetic process and platelet activating factor biosynthetic process. Predicted to be located in Golgi membrane. Predicted to be active in Golgi apparatus and endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHPT1	NM_020244.3	c.629C>A	p.Ala210Glu	missense_variant	Exon 4 of 9	ENST00000229266.8	NP_064629.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHPT1	ENST00000229266.8	c.629C>A	p.Ala210Glu	missense_variant	Exon 4 of 9	1	NM_020244.3	ENSP00000229266.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000404 AC: 1 AN: 247424 Hom.: 0 AF XY: 0.00000747 AC XY: 1 AN XY: 133892

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: 0.00

Gnomad NFE exome AF: 0.00000887

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000620 AC: 9 AN: 1451498 Hom.: 0 Cov.: 27 AF XY: 0.00000415 AC XY: 3 AN XY: 722496

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: 0.00000814

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000508 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0074	T;.
Eigen	Benign	0.091
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.91	D;.
M_CAP	Benign	0.0076	T
MetaRNN	Uncertain	0.60	D;D
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.2	L;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.95	N;N
REVEL	Benign	0.11
Sift	Uncertain	0.0040	D;D
Sift4G	Benign	0.15	T;T
Polyphen		0.29	B;B
Vest4		0.61
MutPred		0.55		Gain of catalytic residue at A206 (P = 0.001);Gain of catalytic residue at A206 (P = 0.001);
MVP		0.76
MPC		0.36
ClinPred		0.51	D
GERP RS		5.5
Varity_R		0.44
gMVP		0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs369936908; hg19: chr12-102110571;