Variant 17-4499263-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_001124758.3(SPNS2):c.216C>T(p.Pro72Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,474,560 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0051 ( 6 hom., cov: 32)

Exomes 𝑓: 0.00055 ( 7 hom. )

Consequence

SPNS2
NM_001124758.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.917

Variant links:

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]

SPNS2 links:

SPNS2-AS1 (HGNC:55787): (SPNS2 antisense RNA 1)

SPNS2-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 17-4499263-C-T is Benign according to our data. Variant chr17-4499263-C-T is described in ClinVar as [Benign]. Clinvar id is 3044738.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.917 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00508 (770/151512) while in subpopulation AFR AF= 0.0177 (731/41358). AF 95% confidence interval is 0.0166. There are 6 homozygotes in gnomad4. There are 363 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPNS2	NM_001124758.3 link	c.216C>T	p.Pro72Pro	synonymous_variant	Exon 1 of 13	ENST00000329078.8	NP_001118230.1	Q8IVW8
SPNS2	XR_007065260.1 link	n.383C>T		non_coding_transcript_exon_variant	Exon 1 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPNS2	ENST00000329078.8 link	c.216C>T	p.Pro72Pro	synonymous_variant	Exon 1 of 13	1	NM_001124758.3	ENSP00000333292.3		Q8IVW8
SPNS2-AS1	ENST00000416958.1 link	n.48+364G>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.00508

AC:

769

AN:

151404

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0177

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000540

AC:

AN:

79668

Hom.:

AF XY:

0.000373

AC XY:

AN XY:

45578

show subpopulations

Gnomad AFR exome

AF:

0.0153

Gnomad AMR exome

AF:

0.00122

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000691

Gnomad OTH exome

AF:

0.00207

GnomAD4 exome

AF:

0.000546

AC:

722

AN:

1323048

Hom.:

Cov.:

AF XY:

0.000501

AC XY:

327

AN XY:

652112

show subpopulations

Gnomad4 AFR exome

AF:

0.0197

Gnomad4 AMR exome

AF:

0.00114

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000137

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000694

Gnomad4 OTH exome

AF:

0.00151

GnomAD4 genome

AF:

0.00508

AC:

770

AN:

151512

Hom.:

Cov.:

AF XY:

0.00490

AC XY:

363

AN XY:

74024

show subpopulations

Gnomad4 AFR

AF:

0.0177

Gnomad4 AMR

AF:

0.00177

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00444

Hom.:

Bravo

AF:

0.00586

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SPNS2-related disorder

Benign:1

Nov 25, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

7.9

DANN

Benign

0.95

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

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