17-4525245-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001124758.3(SPNS2):c.573+52G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00292 in 1,597,644 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (54 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (60 hom.)
• Consequence: SPNS2 NM_001124758.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0370

Genes affected

SPNS2 (HGNC:26992): (SPNS lysolipid transporter 2, sphingosine-1-phosphate) The protein encoded by this gene is a transporter of sphingosine 1-phosphate, a secreted lipid that is important in cardiovascular, immunological, and neural development. Defects in this gene are a cause of early onset progressive hearing loss. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-4525245-G-T is Benign according to our data. Variant chr17-4525245-G-T is described in ClinVar as [Benign]. Clinvar id is 1238088.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPNS2	NM_001124758.3	c.573+52G>T		intron_variant		ENST00000329078.8
SPNS2	XM_047435339.1	c.120+52G>T		intron_variant
SPNS2	XR_007065260.1	n.740+52G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPNS2	ENST00000329078.8	c.573+52G>T		intron_variant		1	NM_001124758.3	P1

Frequencies

GnomAD3 genomes AF: 0.0157 AC: 2392 AN: 152178 Hom.: 54 Cov.: 33

Gnomad AFR AF: 0.0539

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00733

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.0148

GnomAD3 exomes AF: 0.00434 AC: 1044 AN: 240650 Hom.: 21 AF XY: 0.00338 AC XY: 443 AN XY: 130970

Gnomad AFR exome AF: 0.0575

Gnomad AMR exome AF: 0.00404

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000681

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000110

Gnomad OTH exome AF: 0.00170

GnomAD4 exome AF: 0.00157 AC: 2276 AN: 1445348 Hom.: 60 Cov.: 30 AF XY: 0.00131 AC XY: 941 AN XY: 717354

Gnomad4 AFR exome AF: 0.0531

Gnomad4 AMR exome AF: 0.00445

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000200

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000735

Gnomad4 OTH exome AF: 0.00354

GnomAD4 genome AF: 0.0157 AC: 2396 AN: 152296 Hom.: 54 Cov.: 33 AF XY: 0.0153 AC XY: 1138 AN XY: 74474

Gnomad4 AFR AF: 0.0538

Gnomad4 AMR AF: 0.00732

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.000717 Hom.: 2

Bravo AF: 0.0189

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	3.6
Dann	Benign	0.60

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: rs78412357; hg19: chr17-4428540;