NM_001124758.3:c.220_237dupACCCCCGGCACCCCCGGC

Variant names:

• chr17-4499258-C-CCCCCCGGCACCCCCGGCA
• rs763007985
• NM_001124758.3:c.220_237dupACCCCCGGCACCCCCGGC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_001124758.3(SPNS2):​c.220_237dupACCCCCGGCACCCCCGGC​(p.Thr74_Gly79dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000763 in 1,309,946 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: SPNS2 NM_001124758.3 conservative_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.85
• 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.

• PM4: Nonframeshift variant in NON repetitive region in NM_001124758.3.

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.220_237dupACCCCCGGCACCCCCGGC	p.Thr74_Gly79dup	conservative_inframe_insertion	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.220_237dupACCCCCGGCACCCCCGGC	p.Thr74_Gly79dup	conservative_inframe_insertion	Exon 1 of 13	ENSP00000333292.3	Q8IVW8
	SPNS2	ENST00000947403.1		c.220_237dupACCCCCGGCACCCCCGGC	p.Thr74_Gly79dup	conservative_inframe_insertion	Exon 1 of 13	ENSP00000617462.1
	SPNS2	ENST00000932033.1		c.220_237dupACCCCCGGCACCCCCGGC	p.Thr74_Gly79dup	conservative_inframe_insertion	Exon 1 of 12	ENSP00000602092.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.63e-7 AC: 1 AN: 1309946 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 645266

African (AFR) AF: 0.00 AC: 0 AN: 26296

American (AMR) AF: 0.00 AC: 0 AN: 25714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22626

East Asian (EAS) AF: 0.00 AC: 0 AN: 28696

South Asian (SAS) AF: 0.00 AC: 0 AN: 71268

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3952

European-Non Finnish (NFE) AF: 9.57e-7 AC: 1 AN: 1044718

Other (OTH) AF: 0.00 AC: 0 AN: 54294

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.9

Splicing

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

Other links and lift over

dbSNP: rs763007985; hg19: chr17-4402553;