chr10-70834406-G-T

Position:

• chr10-70834406-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003901.4(SGPL1):​c.28-10067G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,208 control chromosomes in the GnomAD database, including 1,325 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 0.12 (1325 hom., cov: 32)
• Consequence: SGPL1 NM_003901.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.529

Genes affected

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGPL1	NM_003901.4	c.28-10067G>T		intron_variant		ENST00000373202.8	NP_003892.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGPL1	ENST00000373202.8	c.28-10067G>T		intron_variant		1	NM_003901.4	ENSP00000362298.3

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18080 AN: 152090 Hom.: 1325 Cov.: 32

Gnomad AFR AF: 0.0419

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.0868

Gnomad SAS AF: 0.0857

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.123

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.119 AC: 18071 AN: 152208 Hom.: 1325 Cov.: 32 AF XY: 0.115 AC XY: 8541 AN XY: 74418

Gnomad4 AFR AF: 0.0418

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.0862

Gnomad4 SAS AF: 0.0847

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.123

Alfa AF: 0.156 Hom.: 2561

Bravo AF: 0.113

Asia WGS AF: 0.0770 AC: 269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.4
DANN	Benign	0.69

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

LitVar

Other links and lift over

dbSNP: rs10509327; hg19: chr10-72594162;