chr3-196239597-G-T

Variant names:

• chr3-196239597-G-T
• rs587777192
• NM_001312673.2:c.847C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001312673.2(PCYT1A):​c.847C>A​(p.Arg283Arg) variant causes a synonymous change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PCYT1A NM_001312673.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.14
• Publications: 5 publications found

Genes affected

PCYT1A (HGNC:8754): (phosphate cytidylyltransferase 1A, choline) This gene belongs to the cytidylyltransferase family and is involved in the regulation of phosphatidylcholine biosynthesis. Mutations in this gene are associated with spondylometaphyseal dysplasia with cone-rod dystrophy. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2015]

SLC51A (HGNC:29955): (solute carrier family 51 member A) Predicted to enable protein heterodimerization activity; protein homodimerization activity; and transmembrane transporter activity. Involved in bile acid secretion. Located in basolateral plasma membrane. Implicated in progressive familial intrahepatic cholestasis. [provided by Alliance of Genome Resources, Apr 2022]

SLC51A Gene-Disease associations (from GenCC):

• cholestasis, progressive familial intrahepatic, 6

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001312673.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCYT1A	NM_001312673.2	MANE Select	c.847C>A	p.Arg283Arg	synonymous	Exon 8 of 9	NP_001299602.1
	PCYT1A	NM_005017.4		c.847C>A	p.Arg283Arg	synonymous	Exon 9 of 10	NP_005008.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCYT1A	ENST00000431016.6	TSL:1 MANE Select	c.847C>A	p.Arg283Arg	synonymous	Exon 8 of 9	ENSP00000394617.1
	PCYT1A	ENST00000292823.6	TSL:1	c.847C>A	p.Arg283Arg	synonymous	Exon 9 of 10	ENSP00000292823.2
	PCYT1A	ENST00000419333.5	TSL:5	c.847C>A	p.Arg283Arg	synonymous	Exon 7 of 9	ENSP00000390968.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	13
DANN	Benign	0.85
PhyloP100		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs587777192; hg19: chr3-195966468;