rs148789676

Variant names:

• chrX-24562362-G-A
• rs148789676
• NM_004845.5:c.1041C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_004845.5(PCYT1B):​c.1041C>T​(p.Pro347Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000841 in 1,175,999 control chromosomes in the GnomAD database, including 1 homozygotes. There are 299 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00055 (0 hom., 16 hem., cov: 23)
  • Exomes 𝑓: 0.00087 (1 hom. 283 hem.)
• Consequence: PCYT1B NM_004845.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.453
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant X-24562362-G-A is Benign according to our data. Variant chrX-24562362-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2660193.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.453 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 16 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCYT1B	NM_004845.5	MANE Select	c.1041C>T	p.Pro347Pro	synonymous	Exon 8 of 8	NP_004836.2
	PCYT1B	NM_001163264.2		c.987C>T	p.Pro329Pro	synonymous	Exon 8 of 8	NP_001156736.1	Q9Y5K3-4
	PCYT1B	NM_001163265.2		c.960+81C>T		intron	N/A	NP_001156737.1	Q9Y5K3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCYT1B	ENST00000379144.7	TSL:1 MANE Select	c.1041C>T	p.Pro347Pro	synonymous	Exon 8 of 8	ENSP00000368439.2	Q9Y5K3-1
	PCYT1B	ENST00000379145.5	TSL:1	c.987C>T	p.Pro329Pro	synonymous	Exon 8 of 8	ENSP00000368440.1	Q9Y5K3-4
	PCYT1B	ENST00000356768.8	TSL:1	c.960+81C>T		intron	N/A	ENSP00000349211.4	Q9Y5K3-2

Frequencies

GnomAD3 genomes AF: 0.000555 AC: 62 AN: 111732 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000372

Gnomad FIN AF: 0.000494

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000809

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000562 AC: 82 AN: 145962 AF XY: 0.000399

Gnomad AFR exome AF: 0.000244

Gnomad AMR exome AF: 0.000447

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000531

Gnomad NFE exome AF: 0.000885

Gnomad OTH exome AF: 0.000573

GnomAD4 exome AF: 0.000871 AC: 927 AN: 1064214 Hom.: 1 Cov.: 30 AF XY: 0.000825 AC XY: 283 AN XY: 342836

African (AFR) AF: 0.000197 AC: 5 AN: 25403

American (AMR) AF: 0.000554 AC: 17 AN: 30674

Ashkenazi Jewish (ASJ) AF: 0.000118 AC: 2 AN: 16909

East Asian (EAS) AF: 0.00 AC: 0 AN: 29916

South Asian (SAS) AF: 0.0000627 AC: 3 AN: 47853

European-Finnish (FIN) AF: 0.000538 AC: 21 AN: 39015

Middle Eastern (MID) AF: 0.00178 AC: 7 AN: 3936

European-Non Finnish (NFE) AF: 0.00100 AC: 829 AN: 825912

Other (OTH) AF: 0.000964 AC: 43 AN: 44596

GnomAD4 genome AF: 0.000555 AC: 62 AN: 111785 Hom.: 0 Cov.: 23 AF XY: 0.000471 AC XY: 16 AN XY: 33965

African (AFR) AF: 0.000130 AC: 4 AN: 30794

American (AMR) AF: 0.00105 AC: 11 AN: 10525

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2642

East Asian (EAS) AF: 0.00 AC: 0 AN: 3538

South Asian (SAS) AF: 0.000374 AC: 1 AN: 2676

European-Finnish (FIN) AF: 0.000494 AC: 3 AN: 6078

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.000810 AC: 43 AN: 53116

Other (OTH) AF: 0.00 AC: 0 AN: 1517

Alfa AF: 0.000696 Hom.: 5

Bravo AF: 0.000793

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	6.8
DANN	Benign	0.62
PhyloP100		-0.45
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs148789676; hg19: chrX-24580479;