Genetic Variant PCYT1B:p.Gln54His (chrX-24619040-C-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_004845.5(PCYT1B):c.162G>C(p.Gln54His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000126 in 1,190,031 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000093 ( 0 hom. 5 hem. )

Consequence

PCYT1B
NM_004845.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.459

Publications

1 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11972046).

BS2

High Hemizygotes in GnomAdExome4 at 5 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004845.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PCYT1B	NM_004845.5	MANE Select	c.162G>C	p.Gln54His	missense	Exon 2 of 8	NP_004836.2
PCYT1B	NM_001163264.2		c.108G>C	p.Gln36His	missense	Exon 2 of 8	NP_001156736.1	Q9Y5K3-4
PCYT1B	NM_001163265.2		c.162G>C	p.Gln54His	missense	Exon 2 of 9	NP_001156737.1	Q9Y5K3-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PCYT1B	ENST00000379144.7	TSL:1 MANE Select	c.162G>C	p.Gln54His	missense	Exon 2 of 8	ENSP00000368439.2	Q9Y5K3-1
PCYT1B	ENST00000379145.5	TSL:1	c.108G>C	p.Gln36His	missense	Exon 2 of 8	ENSP00000368440.1	Q9Y5K3-4
PCYT1B	ENST00000356768.8	TSL:1	c.162G>C	p.Gln54His	missense	Exon 2 of 9	ENSP00000349211.4	Q9Y5K3-2

Frequencies

GnomAD3 genomes

AF:

0.0000448

AC:

AN:

111693

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000325

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000383

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

GnomAD2 exomes

AF:

0.0000238

AC:

AN:

167796

AF XY:

0.0000185

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000157

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000927

AC:

AN:

1078338

Hom.:

Cov.:

AF XY:

0.0000144

AC XY:

AN XY:

347404

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26102

American (AMR)

AF:

0.000235

AC:

AN:

34106

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18613

East Asian (EAS)

AF:

0.00

AC:

AN:

29896

South Asian (SAS)

AF:

0.00

AC:

AN:

50416

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40007

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4061

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

829881

Other (OTH)

AF:

0.0000442

AC:

AN:

45256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000448

AC:

AN:

111693

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33871

show subpopulations

African (AFR)

AF:

0.0000325

AC:

AN:

30731

American (AMR)

AF:

0.000383

AC:

AN:

10455

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2644

East Asian (EAS)

AF:

0.00

AC:

AN:

3572

South Asian (SAS)

AF:

0.00

AC:

AN:

2658

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6042

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53159

Other (OTH)

AF:

0.00

AC:

AN:

1506

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.565

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000223

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.17

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.83

M_CAP

Benign

0.0043

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

0.46

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.2

REVEL

Benign

0.067

Sift

Benign

0.11

Sift4G

Benign

0.12

Polyphen

0.41

Vest4

0.21

MutPred

0.39

Loss of helix (P = 0.0033)

MVP

0.34

MPC

0.0030

ClinPred

0.079

GERP RS

-0.15

Varity_R

0.089

gMVP

0.47

Mutation Taster

=98/2

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over