Genetic Variant NM_001124758.3:c.229_237delACCCCCGGC (chr17-4499258-CCCCCCGGCA-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM4BS2

The NM_001124758.3(SPNS2):c.229_237delACCCCCGGC(p.Thr77_Gly79del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.000662 in 1,461,400 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.00069 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00066 ( 2 hom. )

Consequence

SPNS2
NM_001124758.3 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 3.65

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: Likely_benign. The variant received -2 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001124758.3.

BS2

High Homozygotes in GnomAdExome4 at 2 Unknown,AR gene

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.229_237delACCCCCGGC	p.Thr77_Gly79del	conservative_inframe_deletion	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.229_237delACCCCCGGC	p.Thr77_Gly79del	conservative_inframe_deletion	Exon 1 of 13	ENSP00000333292.3	Q8IVW8
SPNS2	ENST00000947403.1		c.229_237delACCCCCGGC	p.Thr77_Gly79del	conservative_inframe_deletion	Exon 1 of 13	ENSP00000617462.1
SPNS2	ENST00000932033.1		c.229_237delACCCCCGGC	p.Thr77_Gly79del	conservative_inframe_deletion	Exon 1 of 12	ENSP00000602092.1

Frequencies

GnomAD3 genomes

AF:

0.000693

AC:

105

AN:

151438

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00126

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000263

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000605

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000629

AC:

AN:

73108

AF XY:

0.000570

show subpopulations

Gnomad AFR exome

AF:

0.00218

Gnomad AMR exome

AF:

0.000342

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000368

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00101

Gnomad OTH exome

AF:

0.000903

GnomAD4 exome

AF:

0.000658

AC:

862

AN:

1309860

Hom.:

AF XY:

0.000680

AC XY:

439

AN XY:

645230

show subpopulations

African (AFR)

AF:

0.00103

AC:

AN:

26296

American (AMR)

AF:

0.000195

AC:

AN:

25702

Ashkenazi Jewish (ASJ)

AF:

0.0000442

AC:

AN:

22622

East Asian (EAS)

AF:

0.000279

AC:

AN:

28694

South Asian (SAS)

AF:

0.000800

AC:

AN:

71258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32382

Middle Eastern (MID)

AF:

0.000506

AC:

AN:

3952

European-Non Finnish (NFE)

AF:

0.000691

AC:

722

AN:

1044664

Other (OTH)

AF:

0.000737

AC:

AN:

54290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

149

198

248

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

112

140

<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:

0.000693

AC:

105

AN:

151540

Hom.:

Cov.:

AF XY:

0.000676

AC XY:

AN XY:

74016

show subpopulations

African (AFR)

AF:

0.00126

AC:

AN:

41418

American (AMR)

AF:

0.000262

AC:

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3458

East Asian (EAS)

AF:

0.00

AC:

AN:

5114

South Asian (SAS)

AF:

0.00166

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10454

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000605

AC:

AN:

67742

Other (OTH)

AF:

0.00

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000688

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.7

Mutation Taster

=153/47

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over