Genetic Variant SPNS2:p.Gly100Glu (chr17-4499346-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001124758.3(SPNS2):c.299G>A(p.Gly100Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000275 in 1,456,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000023 ( 0 hom. )

Consequence

SPNS2
NM_001124758.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.06

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.121236116).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001124758.3. 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
	SPNS2	NM_001124758.3	MANE Select	c.299G>A	p.Gly100Glu	missense	Exon 1 of 13	NP_001118230.1	Q8IVW8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPNS2	ENST00000329078.8	TSL:1 MANE Select	c.299G>A	p.Gly100Glu	missense	Exon 1 of 13	ENSP00000333292.3	Q8IVW8
SPNS2	ENST00000947403.1		c.299G>A	p.Gly100Glu	missense	Exon 1 of 13	ENSP00000617462.1
SPNS2	ENST00000932033.1		c.299G>A	p.Gly100Glu	missense	Exon 1 of 12	ENSP00000602092.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

69016

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000230

AC:

AN:

1304860

Hom.:

Cov.:

AF XY:

0.00000311

AC XY:

AN XY:

642888

show subpopulations

African (AFR)

AF:

0.0000764

AC:

AN:

26166

American (AMR)

AF:

0.00

AC:

AN:

22750

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21858

East Asian (EAS)

AF:

0.00

AC:

AN:

29532

South Asian (SAS)

AF:

0.00

AC:

AN:

70600

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32182

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5056

European-Non Finnish (NFE)

AF:

9.59e-7

AC:

AN:

1042670

Other (OTH)

AF:

0.00

AC:

AN:

54046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152130

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41466

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67988

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.024

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.68

M_CAP

Pathogenic

0.50

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

4.1

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.58

REVEL

Benign

0.087

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.12

Vest4

0.25

MutPred

0.39

Loss of methylation at R99 (P = 0.0277)

MVP

0.30

MPC

1.0

ClinPred

0.31

GERP RS

2.9

PromoterAI

0.041

Neutral

(source)

Varity_R

0.13

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over