10-70883914-C-T

Position:

chr10-70883914-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000281.4(PCBD1):c.*36G>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 0.752 in 1,598,278 control chromosomes in the GnomAD database, including 453,425 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.75 ( 43064 hom., cov: 31)

Exomes 𝑓: 0.75 ( 410361 hom. )

Consequence

PCBD1
NM_000281.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.411

Variant links:

Genes affected

PCBD1 (HGNC:8646): (pterin-4 alpha-carbinolamine dehydratase 1) This gene encodes a member of the pterin-4-alpha-carbinolamine dehydratase family. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. The encoded protein functions as both a dehydratase involved in tetrahydrobiopterin biosynthesis, and as a cofactor for HNF1A-dependent transcription. A deficiency of this enzyme leads to hyperphenylalaninemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

PCBD1 links:

SGPL1 (HGNC:10817): (sphingosine-1-phosphate lyase 1) Enables sphinganine-1-phosphate aldolase activity. Involved in apoptotic signaling pathway; fatty acid metabolic process; and sphingolipid metabolic process. Located in endoplasmic reticulum. Implicated in nephrotic syndrome type 14. [provided by Alliance of Genome Resources, Apr 2022]

SGPL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 10-70883914-C-T is Benign according to our data. Variant chr10-70883914-C-T is described in ClinVar as [Benign]. Clinvar id is 300345.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
PCBD1	NM_000281.4 linkuse as main transcript	c.*36G>A	3_prime_UTR_variant	4/4	ENST00000299299.4	NP_000272.1
PCBD1	NM_001289797.2 linkuse as main transcript	c.*36G>A	3_prime_UTR_variant	4/4		NP_001276726.1
PCBD1	NM_001323004.2 linkuse as main transcript	c.216+1238G>A	intron_variant			NP_001309933.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
PCBD1	ENST00000299299.4 linkuse as main transcript	c.*36G>A	3_prime_UTR_variant	4/4	1	NM_000281.4	ENSP00000299299	P1
SGPL1	ENST00000697988.1 linkuse as main transcript	c.571-9845C>T	intron_variant				ENSP00000513492
PCBD1	ENST00000493961.5 linkuse as main transcript	n.183+1238G>A	intron_variant, non_coding_transcript_variant		2
PCBD1	ENST00000493228.1 linkuse as main transcript		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.751

AC:

114110

AN:

151866

Hom.:

43027

Cov.:

show subpopulations

Gnomad AFR

AF:

0.741

Gnomad AMI

AF:

0.627

Gnomad AMR

AF:

0.756

Gnomad ASJ

AF:

0.746

Gnomad EAS

AF:

0.782

Gnomad SAS

AF:

0.856

Gnomad FIN

AF:

0.809

Gnomad MID

AF:

0.759

Gnomad NFE

AF:

0.740

Gnomad OTH

AF:

0.730

GnomAD3 exomes

AF:

0.768

AC:

174802

AN:

227516

Hom.:

67272

AF XY:

0.772

AC XY:

94251

AN XY:

122098

show subpopulations

Gnomad AFR exome

AF:

0.739

Gnomad AMR exome

AF:

0.764

Gnomad ASJ exome

AF:

0.756

Gnomad EAS exome

AF:

0.775

Gnomad SAS exome

AF:

0.858

Gnomad FIN exome

AF:

0.806

Gnomad NFE exome

AF:

0.743

Gnomad OTH exome

AF:

0.750

GnomAD4 exome

AF:

0.752

AC:

1088063

AN:

1446294

Hom.:

410361

Cov.:

AF XY:

0.755

AC XY:

541645

AN XY:

717606

show subpopulations

Gnomad4 AFR exome

AF:

0.745

Gnomad4 AMR exome

AF:

0.760

Gnomad4 ASJ exome

AF:

0.755

Gnomad4 EAS exome

AF:

0.800

Gnomad4 SAS exome

AF:

0.852

Gnomad4 FIN exome

AF:

0.803

Gnomad4 NFE exome

AF:

0.741

Gnomad4 OTH exome

AF:

0.749

GnomAD4 genome

AF:

0.751

AC:

114203

AN:

151984

Hom.:

43064

Cov.:

AF XY:

0.759

AC XY:

56384

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.741

Gnomad4 AMR

AF:

0.757

Gnomad4 ASJ

AF:

0.746

Gnomad4 EAS

AF:

0.782

Gnomad4 SAS

AF:

0.857

Gnomad4 FIN

AF:

0.809

Gnomad4 NFE

AF:

0.740

Gnomad4 OTH

AF:

0.732

Alfa

AF:

0.744

Hom.:

15483

Bravo

AF:

0.741

Asia WGS

AF:

0.840

AC:

2920

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 27, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Pterin-4 alpha-carbinolamine dehydratase 1 deficiency

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.7

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over