11-6390705-T-TGGCGCTGGCGCTGGC

Position:

• chr11-6390705-T-TGGCGCTGGCGCTGGC

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_000543.5(SMPD1):​c.108_109insGCGCTGGCGCTGGCG​(p.Val36_Leu37insAlaLeuAlaLeuAla) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V36V) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00025 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: SMPD1 NM_000543.5 inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.158

Genes affected

SMPD1 (HGNC:11120): (sphingomyelin phosphodiesterase 1) The protein encoded by this gene is a lysosomal acid sphingomyelinase that converts sphingomyelin to ceramide. The encoded protein also has phospholipase C activity. Defects in this gene are a cause of Niemann-Pick disease type A (NPA) and Niemann-Pick disease type B (NPB). Multiple transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMPD1	NM_000543.5	c.108_109insGCGCTGGCGCTGGCG	p.Val36_Leu37insAlaLeuAlaLeuAla	inframe_insertion	1/6	ENST00000342245.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMPD1	ENST00000342245.9	c.108_109insGCGCTGGCGCTGGCG	p.Val36_Leu37insAlaLeuAlaLeuAla	inframe_insertion	1/6	1	NM_000543.5	P3

Frequencies

GnomAD3 genomes AF: 0.000163 AC: 24 AN: 147228 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000748

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000674

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00129

Gnomad FIN AF: 0.0000986

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000197

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000251 AC: 364 AN: 1447756 Hom.: 2 Cov.: 0 AF XY: 0.000307 AC XY: 221 AN XY: 720012

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000113

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000456

Gnomad4 SAS exome AF: 0.00171

Gnomad4 FIN exome AF: 0.0000966

Gnomad4 NFE exome AF: 0.000156

Gnomad4 OTH exome AF: 0.000268

GnomAD4 genome AF: 0.000163 AC: 24 AN: 147354 Hom.: 0 Cov.: 0 AF XY: 0.000167 AC XY: 12 AN XY: 71998

Gnomad4 AFR AF: 0.0000746

Gnomad4 AMR AF: 0.0000673

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00129

Gnomad4 FIN AF: 0.0000986

Gnomad4 NFE AF: 0.000197

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs775568984; hg19: chr11-6411935;