Variant rs761363750 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000543.5(SMPD1):c.107_118delTGCTGGCGCTGG(p.Val36_Leu39del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0753 in 1,546,630 control chromosomes in the GnomAD database, including 4,521 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 331 hom., cov: 0)

Exomes 𝑓: 0.076 ( 4190 hom. )

Consequence

SMPD1
NM_000543.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 1.67

Variant links:

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]

SMPD1 links:

SMPD1 (HGNC:):

SMPD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 11-6390700-CCTGGTGCTGGCG-C is Benign according to our data. Variant chr11-6390700-CCTGGTGCTGGCG-C is described in ClinVar as [Benign]. Clinvar id is 193113.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-6390700-CCTGGTGCTGGCG-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMPD1	NM_000543.5 linkuse as main transcript	c.107_118delTGCTGGCGCTGG	p.Val36_Leu39del	disruptive_inframe_deletion	1/6	ENST00000342245.9	NP_000534.3	P17405-1Q59EN6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMPD1	ENST00000342245.9 linkuse as main transcript	c.107_118delTGCTGGCGCTGG	p.Val36_Leu39del	disruptive_inframe_deletion	1/6	1	NM_000543.5	ENSP00000340409.4		P17405-1

Frequencies

GnomAD3 genomes

AF:

0.0631

AC:

8772

AN:

139088

Hom.:

332

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0185

Gnomad AMI

AF:

0.0443

Gnomad AMR

AF:

0.0493

Gnomad ASJ

AF:

0.0877

Gnomad EAS

AF:

0.0680

Gnomad SAS

AF:

0.0780

Gnomad FIN

AF:

0.106

Gnomad MID

AF:

0.0971

Gnomad NFE

AF:

0.0840

Gnomad OTH

AF:

0.0717

GnomAD3 exomes

AF:

0.0703

AC:

16351

AN:

232506

Hom.:

641

AF XY:

0.0722

AC XY:

9169

AN XY:

126968

show subpopulations

Gnomad AFR exome

AF:

0.0149

Gnomad AMR exome

AF:

0.0367

Gnomad ASJ exome

AF:

0.0920

Gnomad EAS exome

AF:

0.0691

Gnomad SAS exome

AF:

0.0693

Gnomad FIN exome

AF:

0.0981

Gnomad NFE exome

AF:

0.0820

Gnomad OTH exome

AF:

0.0732

GnomAD4 exome

AF:

0.0765

AC:

107636

AN:

1407438

Hom.:

4190

AF XY:

0.0764

AC XY:

53525

AN XY:

700294

show subpopulations

Gnomad4 AFR exome

AF:

0.0144

Gnomad4 AMR exome

AF:

0.0389

Gnomad4 ASJ exome

AF:

0.0934

Gnomad4 EAS exome

AF:

0.0632

Gnomad4 SAS exome

AF:

0.0678

Gnomad4 FIN exome

AF:

0.0960

Gnomad4 NFE exome

AF:

0.0799

Gnomad4 OTH exome

AF:

0.0728

GnomAD4 genome

AF:

0.0630

AC:

8773

AN:

139192

Hom.:

331

Cov.:

AF XY:

0.0630

AC XY:

4263

AN XY:

67702

show subpopulations

Gnomad4 AFR

AF:

0.0185

Gnomad4 AMR

AF:

0.0492

Gnomad4 ASJ

AF:

0.0877

Gnomad4 EAS

AF:

0.0683

Gnomad4 SAS

AF:

0.0776

Gnomad4 FIN

AF:

0.106

Gnomad4 NFE

AF:

0.0840

Gnomad4 OTH

AF:

0.0730

Alfa

AF:

0.0430

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Dec 20, 2021	Variant summary: SMPD1 c.107_118del12 (p.Val36_Leu39del) results in an in-frame deletion that is predicted to remove four amino acids from the encoded protein. The variant allele was found at a frequency of 0.07 in 232506 control chromosomes in the gnomAD database, including 641 homozygotes. The observed variant frequency is approximately 31.45 fold of the estimated maximal expected allele frequency for a pathogenic variant in SMPD1 causing Niemann-Pick Disease Type A phenotype (0.0022), strongly suggesting that the variant is benign. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign. -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 22, 2015	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	Mar 24, 2016	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	May 02, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 01, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

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

Feb 01, 2024

- -

Niemann-Pick disease, type A

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

May 06, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over