NM_003901.4:c.144G>T

Variant names:

• chr10-70844589-G-T
• rs754308801
• NM_003901.4:c.144G>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_003901.4(SGPL1):​c.144G>T​(p.Val48Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. V48V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000034 (0 hom.)
• Consequence: SGPL1 NM_003901.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.344
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• nephrotic syndrome 14

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

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 10-70844589-G-T is Benign according to our data. Variant chr10-70844589-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2971252.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.344 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003901.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGPL1	NM_003901.4	MANE Select	c.144G>T	p.Val48Val	synonymous	Exon 3 of 15	NP_003892.2
	SGPL1	NM_001437828.1		c.-97G>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 14	NP_001424757.1	A0A8V8TN35
	SGPL1	NM_001438353.1		c.144G>T	p.Val48Val	synonymous	Exon 3 of 16	NP_001425282.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGPL1	ENST00000373202.8	TSL:1 MANE Select	c.144G>T	p.Val48Val	synonymous	Exon 3 of 15	ENSP00000362298.3	O95470
	SGPL1	ENST00000697926.1		c.-97G>T		5_prime_UTR_premature_start_codon_gain	Exon 4 of 16	ENSP00000513480.1	A0A8V8TN35
	SGPL1	ENST00000697927.1		c.-97G>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 14	ENSP00000513481.1	A0A8V8TN35

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251438 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000335 AC: 49 AN: 1461854 Hom.: 0 Cov.: 31 AF XY: 0.0000261 AC XY: 19 AN XY: 727224

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000432 AC: 48 AN: 1111994

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000474 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.1
DANN	Benign	0.74
PhyloP100		0.34
PromoterAI		0.017	Neutral

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: rs754308801; hg19: chr10-72604346;