3-196237816-C-T

Variant names:

• chr3-196237816-C-T
• rs712012
• NM_001312673.2:c.*872G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001312673.2(PCYT1A):​c.*872G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.699 in 152,138 control chromosomes in the GnomAD database, including 38,127 homozygotes. 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: 𝑓 0.70 (38126 hom., cov: 32)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: PCYT1A NM_001312673.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06
• Publications: 10 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCYT1A	NM_001312673.2	c.*872G>A		3_prime_UTR_variant	Exon 9 of 9	ENST00000431016.6	NP_001299602.1
PCYT1A	NM_005017.4	c.*872G>A		3_prime_UTR_variant	Exon 10 of 10		NP_005008.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCYT1A	ENST00000431016.6	c.*872G>A		3_prime_UTR_variant	Exon 9 of 9	1	NM_001312673.2	ENSP00000394617.1

Frequencies

GnomAD3 genomes AF: 0.699 AC: 106309 AN: 152016 Hom.: 38073 Cov.: 32

Gnomad AFR AF: 0.842

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.712

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.871

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.619

Gnomad OTH AF: 0.692

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 2 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.699 AC: 106415 AN: 152134 Hom.: 38126 Cov.: 32 AF XY: 0.702 AC XY: 52179 AN XY: 74352

African (AFR) AF: 0.842 AC: 34962 AN: 41532

American (AMR) AF: 0.712 AC: 10882 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 2322 AN: 3472

East Asian (EAS) AF: 0.871 AC: 4518 AN: 5186

South Asian (SAS) AF: 0.628 AC: 3029 AN: 4822

European-Finnish (FIN) AF: 0.609 AC: 6430 AN: 10556

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.619 AC: 42096 AN: 67966

Other (OTH) AF: 0.693 AC: 1464 AN: 2112

Alfa AF: 0.643 Hom.: 39188

Bravo AF: 0.716

Asia WGS AF: 0.747 AC: 2595 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.046
DANN	Benign	0.61
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs712012; hg19: chr3-195964687;