chr11-6390705-T-TGGCGCTGGC

Position:

• chr11-6390705-T-TGGCGCTGGC

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_000543.5(SMPD1):​c.108_109insGCGCTGGCG​(p.Val36_Leu37insAlaLeuAla) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (19 hom., cov: 0)
  • Exomes 𝑓: 0.014 (173 hom.)
  • Failed GnomAD Quality Control
• Consequence: SMPD1 NM_000543.5 inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B:2
• 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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 11-6390705-T-TGGCGCTGGC is Benign according to our data. Variant chr11-6390705-T-TGGCGCTGGC is described in ClinVar as [Benign]. Clinvar id is 1170921.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMPD1	NM_000543.5	c.108_109insGCGCTGGCG	p.Val36_Leu37insAlaLeuAla	inframe_insertion	1/6	ENST00000342245.9	NP_000534.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMPD1	ENST00000342245.9	c.108_109insGCGCTGGCG	p.Val36_Leu37insAlaLeuAla	inframe_insertion	1/6	1	NM_000543.5	ENSP00000340409	P3

Frequencies

GnomAD3 genomes AF: 0.0110 AC: 1625 AN: 147226 Hom.: 19 Cov.: 0

Gnomad AFR AF: 0.00314

Gnomad AMI AF: 0.0763

Gnomad AMR AF: 0.00519

Gnomad ASJ AF: 0.000593

Gnomad EAS AF: 0.0102

Gnomad SAS AF: 0.0147

Gnomad FIN AF: 0.0357

Gnomad MID AF: 0.0136

Gnomad NFE AF: 0.0129

Gnomad OTH AF: 0.00941

GnomAD3 exomes AF: 0.0115 AC: 2742 AN: 238972 Hom.: 41 AF XY: 0.0119 AC XY: 1549 AN XY: 130606

Gnomad AFR exome AF: 0.00190

Gnomad AMR exome AF: 0.00320

Gnomad ASJ exome AF: 0.000816

Gnomad EAS exome AF: 0.00992

Gnomad SAS exome AF: 0.0146

Gnomad FIN exome AF: 0.0212

Gnomad NFE exome AF: 0.0139

Gnomad OTH exome AF: 0.0108

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0135 AC: 19560 AN: 1447704 Hom.: 173 Cov.: 0 AF XY: 0.0134 AC XY: 9671 AN XY: 719976

Gnomad4 AFR exome AF: 0.00211

Gnomad4 AMR exome AF: 0.00363

Gnomad4 ASJ exome AF: 0.00101

Gnomad4 EAS exome AF: 0.00785

Gnomad4 SAS exome AF: 0.0149

Gnomad4 FIN exome AF: 0.0285

Gnomad4 NFE exome AF: 0.0141

Gnomad4 OTH exome AF: 0.0110

GnomAD4 genome AF: 0.0110 AC: 1626 AN: 147352 Hom.: 19 Cov.: 0 AF XY: 0.0117 AC XY: 841 AN XY: 71996

Gnomad4 AFR AF: 0.00313

Gnomad4 AMR AF: 0.00518

Gnomad4 ASJ AF: 0.000593

Gnomad4 EAS AF: 0.0102

Gnomad4 SAS AF: 0.0146

Gnomad4 FIN AF: 0.0357

Gnomad4 NFE AF: 0.0129

Gnomad4 OTH AF: 0.00930

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Niemann-Pick disease, type A;C0268243:Niemann-Pick disease, type B Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 27, 2023

- -

Niemann-Pick disease, type A Benign:1

Likely benign, no assertion criteria provided

clinical testing

Natera, Inc.

Aug 09, 2017

- -

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;