rs1260715912

Variant names:

• chr17-4499063-T-C
• rs1260715912
• NM_001124758.3:c.16T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001124758.3(SPNS2):​c.16T>C​(p.Cys6Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000266 in 1,015,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: SPNS2 NM_001124758.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0910
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0913021).

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.16T>C	p.Cys6Arg	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.16T>C	p.Cys6Arg	missense	Exon 1 of 13	ENSP00000333292.3	Q8IVW8
	SPNS2	ENST00000947403.1		c.16T>C	p.Cys6Arg	missense	Exon 1 of 13	ENSP00000617462.1
	SPNS2	ENST00000932033.1		c.16T>C	p.Cys6Arg	missense	Exon 1 of 12	ENSP00000602092.1

Frequencies

GnomAD3 genomes AF: 0.0000205 AC: 3 AN: 146676 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000455

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000276 AC: 24 AN: 868924 Hom.: 0 Cov.: 29 AF XY: 0.0000321 AC XY: 13 AN XY: 405194

African (AFR) AF: 0.00 AC: 0 AN: 16450

American (AMR) AF: 0.00 AC: 0 AN: 2302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5958

East Asian (EAS) AF: 0.00 AC: 0 AN: 4902

South Asian (SAS) AF: 0.00 AC: 0 AN: 17626

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4242

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1782

European-Non Finnish (NFE) AF: 0.0000293 AC: 23 AN: 786220

Other (OTH) AF: 0.0000340 AC: 1 AN: 29442

GnomAD4 genome AF: 0.0000205 AC: 3 AN: 146676 Hom.: 0 Cov.: 32 AF XY: 0.0000280 AC XY: 2 AN XY: 71314

African (AFR) AF: 0.00 AC: 0 AN: 40758

American (AMR) AF: 0.00 AC: 0 AN: 14796

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3394

East Asian (EAS) AF: 0.00 AC: 0 AN: 5010

South Asian (SAS) AF: 0.00 AC: 0 AN: 4718

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8758

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000455 AC: 3 AN: 65984

Other (OTH) AF: 0.00 AC: 0 AN: 2036

Alfa AF: 0.000142 Hom.: 0

ClinVar

ClinVar submissions

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	0.30
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Uncertain	24
DANN	Benign	0.79
DEOGEN2	Benign	0.042	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.34	T
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.091
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.021
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.12	B
Vest4		0.13
MutPred		0.31		Gain of MoRF binding (P = 0.0036)
MVP		0.16
MPC		1.4
ClinPred		0.16	T
GERP RS		1.8
PromoterAI		-0.090	Neutral
Varity_R		0.82
Mutation Taster		=88/12	polymorphism

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: rs1260715912; hg19: chr17-4402358;