rs827241

Variant names:

• chr10-70887896-G-C
• rs827241
• NM_000281.4:c.3+635C>G

Your query was ambiguous. Multiple possible variants found:

• chr10-70887896-G-C
• chr10-70887896-G-T

Variant summary

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

The NM_000281.4(PCBD1):​c.3+635C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,346 control chromosomes in the GnomAD database, including 2,243 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 0.16 (2237 hom., cov: 32)
  • Exomes 𝑓: 0.20 (6 hom.)
• Consequence: PCBD1 NM_000281.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.326
• Publications: 2 publications found

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]

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 Gene-Disease associations (from GenCC):

• nephrotic syndrome 14

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000281.4. 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
	PCBD1	NM_000281.4	MANE Select	c.3+635C>G		intron	N/A	NP_000272.1
	PCBD1	NM_001323004.2		c.3+635C>G		intron	N/A	NP_001309933.1
	PCBD1	NM_001289797.2		c.-188C>G		upstream_gene	N/A	NP_001276726.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCBD1	ENST00000299299.4	TSL:1 MANE Select	c.3+635C>G		intron	N/A	ENSP00000299299.3
	PCBD1	ENST00000493228.1	TSL:2	n.359C>G		non_coding_transcript_exon	Exon 1 of 4
	SGPL1	ENST00000697988.1		c.571-5863G>C		intron	N/A	ENSP00000513492.1

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24700 AN: 151970 Hom.: 2241 Cov.: 32

Gnomad AFR AF: 0.0823

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.0755

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.185

GnomAD4 exome AF: 0.202 AC: 52 AN: 258 Hom.: 6 Cov.: 0 AF XY: 0.184 AC XY: 36 AN XY: 196

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 2 AN: 4

East Asian (EAS) AF: 0.125 AC: 1 AN: 8

South Asian (SAS) AF: 0.100 AC: 1 AN: 10

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AF: 0.250 AC: 1 AN: 4

European-Non Finnish (NFE) AF: 0.209 AC: 43 AN: 206

Other (OTH) AF: 0.167 AC: 3 AN: 18

GnomAD4 genome AF: 0.162 AC: 24690 AN: 152088 Hom.: 2237 Cov.: 32 AF XY: 0.163 AC XY: 12110 AN XY: 74344

African (AFR) AF: 0.0821 AC: 3411 AN: 41524

American (AMR) AF: 0.190 AC: 2900 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 485 AN: 3470

East Asian (EAS) AF: 0.0755 AC: 388 AN: 5140

South Asian (SAS) AF: 0.117 AC: 566 AN: 4822

European-Finnish (FIN) AF: 0.249 AC: 2633 AN: 10578

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13674 AN: 67944

Other (OTH) AF: 0.183 AC: 387 AN: 2110

Alfa AF: 0.0997 Hom.: 135

Bravo AF: 0.160

Asia WGS AF: 0.0830 AC: 287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.36
PhyloP100		0.33
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: rs827241; hg19: chr10-72647653;