rs1395107719

Variant names:

• chr17-4499343-G-A
• rs1395107719
• NM_001124758.3:c.296G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-4499343-G-A
• chr17-4499343-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001124758.3(SPNS2):​c.296G>A​(p.Arg99His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPNS2 NM_001124758.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.99
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.296G>A	p.Arg99His	missense	Exon 1 of 13	NP_001118230.1	Q8IVW8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPNS2	ENST00000329078.8	TSL:1 MANE Select	c.296G>A	p.Arg99His	missense	Exon 1 of 13	ENSP00000333292.3	Q8IVW8
	SPNS2	ENST00000947403.1		c.296G>A	p.Arg99His	missense	Exon 1 of 13	ENSP00000617462.1
	SPNS2	ENST00000932033.1		c.296G>A	p.Arg99His	missense	Exon 1 of 12	ENSP00000602092.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1304800 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 642780

African (AFR) AF: 0.00 AC: 0 AN: 26188

American (AMR) AF: 0.00 AC: 0 AN: 23180

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21960

East Asian (EAS) AF: 0.00 AC: 0 AN: 29454

South Asian (SAS) AF: 0.00 AC: 0 AN: 70540

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32136

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5038

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1042208

Other (OTH) AF: 0.00 AC: 0 AN: 54096

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Pathogenic	31
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.065	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.80	T
M_CAP	Pathogenic	0.93	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.0	N
PhyloP100		5.0
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.13
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.021	D
Polyphen		1.0	D
Vest4		0.25
MutPred		0.40		Loss of methylation at R99 (P = 0.0112)
MVP		0.60
MPC		1.9
ClinPred		0.77	D
GERP RS		3.0
PromoterAI		-0.035	Neutral
Varity_R		0.19

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: rs1395107719; hg19: chr17-4402638;