X-24619030-G-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_004845.5(PCYT1B):c.172C>A(p.Pro58Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000233 in 1,074,571 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.000023 (0 hom. 12 hem.)
• Consequence: PCYT1B NM_004845.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.46

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.113711715).
• BS2: High Hemizygotes in GnomAdExome at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCYT1B	NM_004845.5	c.172C>A	p.Pro58Thr	missense_variant	2/8	ENST00000379144.7
PCYT1B	NM_001163264.2	c.118C>A	p.Pro40Thr	missense_variant	2/8
PCYT1B	NM_001163265.2	c.172C>A	p.Pro58Thr	missense_variant	2/9
PCYT1B	XM_017029977.2	c.-117C>A		5_prime_UTR_variant	3/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCYT1B	ENST00000379144.7	c.172C>A	p.Pro58Thr	missense_variant	2/8	1	NM_004845.5	P1
PCYT1B	ENST00000379145.5	c.118C>A	p.Pro40Thr	missense_variant	2/8	1
PCYT1B	ENST00000356768.8	c.172C>A	p.Pro58Thr	missense_variant	2/9	1
PCYT1B	ENST00000496020.1	c.94C>A	p.Pro32Thr	missense_variant, NMD_transcript_variant	2/7	3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD3 exomes AF: 0.0000788 AC: 13 AN: 165022 Hom.: 0 AF XY: 0.000115 AC XY: 6 AN XY: 52346

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: 0.000956

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000233 AC: 25 AN: 1074571 Hom.: 0 Cov.: 26 AF XY: 0.0000348 AC XY: 12 AN XY: 345107

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: 0.000444

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000665

GnomAD4 genome Cov.: 22

ExAC AF: 0.0000824 AC: 10

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 15, 2021

The c.172C>A (p.P58T) alteration is located in exon 2 (coding exon 2) of the PCYT1B gene. This alteration results from a C to A substitution at nucleotide position 172, causing the proline (P) at amino acid position 58 to be replaced by a threonine (T). 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	0.11
BayesDel_addAF	Uncertain	0.038	T
BayesDel_noAF	Pathogenic	0.22
Cadd	Uncertain	23
Dann	Uncertain	0.97
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-0.91	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.080	N;N;N
REVEL	Uncertain	0.31
Sift	Benign	0.34	T;T;T
Sift4G	Benign	0.56	T;T;T
Polyphen		0.0020, 0.0030	.;B;B
Vest4		0.40
MutPred		0.38		.;Gain of helix (P = 0.0143);Gain of helix (P = 0.0143);
MVP		0.84
MPC		0.0028
ClinPred		0.29	T
GERP RS		5.0
Varity_R		0.29
gMVP		0.77

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: rs758818593; hg19: chrX-24637147;