12-101714234-A-C

Variant names:

• chr12-101714234-A-C
• rs757509848
• NM_020244.3:c.418A>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_020244.3(CHPT1):​c.418A>C​(p.Thr140Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000907 in 1,432,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 0.0000091 (0 hom.)
• Consequence: CHPT1 NM_020244.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.92

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.803

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHPT1	NM_020244.3	c.418A>C	p.Thr140Pro	missense_variant	Exon 2 of 9	ENST00000229266.8	NP_064629.2
CHPT1	XM_011538574.2	c.418A>C	p.Thr140Pro	missense_variant	Exon 2 of 8		XP_011536876.1
CHPT1	XR_001748818.2	n.640A>C		non_coding_transcript_exon_variant	Exon 2 of 8
CHPT1	XR_245946.3	n.640A>C		non_coding_transcript_exon_variant	Exon 2 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHPT1	ENST00000229266.8	c.418A>C	p.Thr140Pro	missense_variant	Exon 2 of 9	1	NM_020244.3	ENSP00000229266.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000443 AC: 10 AN: 225714 Hom.: 0 AF XY: 0.0000410 AC XY: 5 AN XY: 122066

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: 0.0000938

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000907 AC: 13 AN: 1432724 Hom.: 0 Cov.: 30 AF XY: 0.00000843 AC XY: 6 AN XY: 711524

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: 0.0000118

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000741 AC: 9

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Uncertain	0.071	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T;.
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.96	D;.
M_CAP	Benign	0.020	T
MetaRNN	Pathogenic	0.80	D;D
MetaSVM	Benign	-0.57	T
MutationAssessor	Pathogenic	3.5	M;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-5.3	D;D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.0070	D;D
Polyphen		1.0	D;D
Vest4		0.73
MutPred		0.56		Gain of catalytic residue at A144 (P = 8e-04);Gain of catalytic residue at A144 (P = 8e-04);
MVP		0.75
MPC		1.1
ClinPred		0.94	D
GERP RS		4.7
Varity_R		0.87
gMVP		0.88

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: rs757509848; hg19: chr12-102108012;