Genetic Variant NM_001312673.2:c.*444T>A (chr3-196238244-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001312673.2(PCYT1A):c.*444T>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 0.652 in 153,608 control chromosomes in the GnomAD database, including 33,041 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 0.65 ( 32765 hom., cov: 33)

Exomes 𝑓: 0.60 ( 276 hom. )

Consequence

PCYT1A
NM_001312673.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0190

Publications

2 publications found

Variant links:

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]

PCYT1A links:

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)

SLC51A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCYT1A	NM_001312673.2 link	c.*444T>A		3_prime_UTR_variant	Exon 9 of 9	ENST00000431016.6	NP_001299602.1	P49585B4E322
PCYT1A	NM_005017.4 link	c.*444T>A		3_prime_UTR_variant	Exon 10 of 10		NP_005008.2	P49585

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCYT1A	ENST00000431016.6 link	c.*444T>A		3_prime_UTR_variant	Exon 9 of 9	1	NM_001312673.2	ENSP00000394617.1		P49585

Frequencies

GnomAD3 genomes

AF:

0.653

AC:

99239

AN:

152012

Hom.:

32719

Cov.:

show subpopulations

Gnomad AFR

AF:

0.672

Gnomad AMI

AF:

0.562

Gnomad AMR

AF:

0.693

Gnomad ASJ

AF:

0.666

Gnomad EAS

AF:

0.887

Gnomad SAS

AF:

0.633

Gnomad FIN

AF:

0.607

Gnomad MID

AF:

0.693

Gnomad NFE

AF:

0.623

Gnomad OTH

AF:

0.660

GnomAD4 exome

AF:

0.598

AC:

884

AN:

1478

Hom.:

276

Cov.:

AF XY:

0.581

AC XY:

439

AN XY:

756

show subpopulations

African (AFR)

AF:

0.673

AC:

AN:

American (AMR)

AF:

0.731

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.591

AC:

AN:

East Asian (EAS)

AF:

0.864

AC:

AN:

South Asian (SAS)

AF:

0.650

AC:

AN:

European-Finnish (FIN)

AF:

0.598

AC:

286

AN:

478

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.586

AC:

442

AN:

754

Other (OTH)

AF:

0.550

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.653

AC:

99339

AN:

152130

Hom.:

32765

Cov.:

AF XY:

0.657

AC XY:

48857

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.673

AC:

27892

AN:

41472

American (AMR)

AF:

0.693

AC:

10593

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.666

AC:

2308

AN:

3468

East Asian (EAS)

AF:

0.888

AC:

4603

AN:

5186

South Asian (SAS)

AF:

0.633

AC:

3050

AN:

4822

European-Finnish (FIN)

AF:

0.607

AC:

6422

AN:

10576

Middle Eastern (MID)

AF:

0.701

AC:

206

AN:

294

European-Non Finnish (NFE)

AF:

0.623

AC:

42357

AN:

68000

Other (OTH)

AF:

0.661

AC:

1397

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1788

3575

5363

7150

8938

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.517

Hom.:

1368

Bravo

AF:

0.664

Asia WGS

AF:

0.743

AC:

2581

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

5.9

(source)

DANN

Benign

0.63

PhyloP100

0.019

Mutation Taster

=100/0

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

NM_001312673.2:c.*444T>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over