Variant X-24562475-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004845.5(PCYT1B):c.928A>C(p.Met310Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000916 in 1,091,149 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 9.2e-7 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

PCYT1B
NM_004845.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.72

Variant links:

Genes affected

PCYT1B (HGNC:8755): (phosphate cytidylyltransferase 1B, choline) The protein encoded by this gene belongs to the cytidylyltransferase family. It is involved in the regulation of phosphatidylcholine biosynthesis. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

PCYT1B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2500484).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PCYT1B	NM_004845.5 linkuse as main transcript	c.928A>C	p.Met310Leu	missense_variant	8/8	ENST00000379144.7
PCYT1B	NM_001163264.2 linkuse as main transcript	c.874A>C	p.Met292Leu	missense_variant	8/8
PCYT1B	NM_001163265.2 linkuse as main transcript	c.928A>C	p.Met310Leu	missense_variant	8/9
PCYT1B	XM_017029977.2 linkuse as main transcript	c.640A>C	p.Met214Leu	missense_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCYT1B	ENST00000379144.7 linkuse as main transcript	c.928A>C	p.Met310Leu	missense_variant	8/8	1	NM_004845.5	P1	Q9Y5K3-1
PCYT1B	ENST00000379145.5 linkuse as main transcript	c.874A>C	p.Met292Leu	missense_variant	8/8	1			Q9Y5K3-4
PCYT1B	ENST00000356768.8 linkuse as main transcript	c.928A>C	p.Met310Leu	missense_variant	8/9	1			Q9Y5K3-2
PCYT1B	ENST00000496020.1 linkuse as main transcript	c.*237A>C		3_prime_UTR_variant, NMD_transcript_variant	7/7	3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

111530

Hom.:

Cov.:

AF XY:

0.0000297

AC XY:

AN XY:

33714

FAILED QC

Gnomad AFR

AF:

0.0000326

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

9.16e-7

AC:

AN:

1091149

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

357185

show subpopulations

Gnomad4 AFR exome

AF:

0.0000380

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000897

AC:

AN:

111530

Hom.:

Cov.:

AF XY:

0.0000297

AC XY:

AN XY:

33714

show subpopulations

Gnomad4 AFR

AF:

0.0000326

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 04, 2023

The c.928A>C (p.M310L) alteration is located in exon 8 (coding exon 8) of the PCYT1B gene. This alteration results from a A to C substitution at nucleotide position 928, causing the methionine (M) at amino acid position 310 to be replaced by a leucine (L). 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

0.17

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.040

CADD

Benign

DANN

Benign

0.92

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

0.97

D;D;D

M_CAP

Benign

0.028

MetaRNN

Benign

0.25

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.73

PROVEAN

Benign

0.61

N;N;N

REVEL

Benign

0.18

Sift

Benign

0.59

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0, 0.014

.;B;B

Vest4

0.48

MutPred

0.30

.;Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);

MVP

0.88

MPC

1.2

ClinPred

0.61

GERP RS

5.7

Varity_R

0.52

gMVP

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over