chr17-4499258-CCCCCCGGCA-C
Variant summary
Our verdict is Likely benign. Variant got -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
Consequence
NM_001124758.3 conservative_inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SPNS2 | NM_001124758.3 | c.229_237delACCCCCGGC | p.Thr77_Gly79del | conservative_inframe_deletion | Exon 1 of 13 | ENST00000329078.8 | NP_001118230.1 | |
SPNS2 | XR_007065260.1 | n.396_404delACCCCCGGC | non_coding_transcript_exon_variant | Exon 1 of 13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SPNS2 | ENST00000329078.8 | c.229_237delACCCCCGGC | p.Thr77_Gly79del | conservative_inframe_deletion | Exon 1 of 13 | 1 | NM_001124758.3 | ENSP00000333292.3 | ||
SPNS2-AS1 | ENST00000416958.1 | n.48+360_48+368delTGCCGGGGG | intron_variant | Intron 1 of 1 | 3 |
Frequencies
GnomAD3 genomes AF: 0.000693 AC: 105AN: 151438Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000629 AC: 46AN: 73108Hom.: 0 AF XY: 0.000570 AC XY: 24AN XY: 42088
GnomAD4 exome AF: 0.000658 AC: 862AN: 1309860Hom.: 2 AF XY: 0.000680 AC XY: 439AN XY: 645230
GnomAD4 genome AF: 0.000693 AC: 105AN: 151540Hom.: 0 Cov.: 32 AF XY: 0.000676 AC XY: 50AN XY: 74016
ClinVar
Submissions by phenotype
not provided Uncertain:1
The SPNS2 p.Thr77_Gly79del variant was not identified in the literature nor was it identified in ClinVar. The variant was identified in dbSNP (ID: rs763007985) and in control databases in 65 of 103722 chromosomes at a frequency of 0.0006267 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: African in 11 of 9494 chromosomes (freq: 0.001159), European (non-Finnish) in 36 of 41774 chromosomes (freq: 0.000862), Other in 2 of 3262 chromosomes (freq: 0.000613), South Asian in 9 of 15700 chromosomes (freq: 0.000573), Latino in 6 of 15438 chromosomes (freq: 0.000389) and East Asian in 1 of 4272 chromosomes (freq: 0.000234), but was not observed in the Ashkenazi Jewish or European (Finnish) populations. This variant is an in-frame deletion resulting in the removal codons 77 to 79; the impact of this alteration on SPNS2 protein function is not known. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at