dbSNP rs550067660: SMPD1:p.Val36_Leu43del (chr11-6390700-CCTGGTGCTGGCGCTGGCGCTGGCG-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_000543.5(SMPD1):c.107_130delTGCTGGCGCTGGCGCTGGCGCTGG(p.Val36_Leu43del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00125 in 1,546,828 control chromosomes in the GnomAD database, including 13 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00098 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0013 ( 13 hom. )

Consequence

SMPD1
NM_000543.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP6

Variant 11-6390700-CCTGGTGCTGGCGCTGGCGCTGGCG-C is Benign according to our data. Variant chr11-6390700-CCTGGTGCTGGCGCTGGCGCTGGCG-C is described in ClinVar as [Likely_benign]. Clinvar id is 459633.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMPD1	NM_000543.5 link	c.107_130delTGCTGGCGCTGGCGCTGGCGCTGG	p.Val36_Leu43del	disruptive_inframe_deletion	Exon 1 of 6	ENST00000342245.9	NP_000534.3	P17405-1Q59EN6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMPD1	ENST00000342245.9 link	c.107_130delTGCTGGCGCTGGCGCTGGCGCTGG	p.Val36_Leu43del	disruptive_inframe_deletion	Exon 1 of 6	1	NM_000543.5	ENSP00000340409.4		P17405-1

Frequencies

GnomAD3 genomes

AF:

0.000970

AC:

135

AN:

139132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000159

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000909

Gnomad ASJ

AF:

0.00387

Gnomad EAS

AF:

0.000415

Gnomad SAS

AF:

0.00713

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00719

Gnomad NFE

AF:

0.00110

Gnomad OTH

AF:

0.000527

GnomAD3 exomes

AF:

0.00188

AC:

437

AN:

232506

Hom.:

AF XY:

0.00202

AC XY:

256

AN XY:

126968

show subpopulations

Gnomad AFR exome

AF:

0.000485

Gnomad AMR exome

AF:

0.00155

Gnomad ASJ exome

AF:

0.00299

Gnomad EAS exome

AF:

0.000466

Gnomad SAS exome

AF:

0.00725

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00120

Gnomad OTH exome

AF:

0.00140

GnomAD4 exome

AF:

0.00127

AC:

1792

AN:

1407592

Hom.:

AF XY:

0.00147

AC XY:

1032

AN XY:

700352

show subpopulations

Gnomad4 AFR exome

AF:

0.000483

Gnomad4 AMR exome

AF:

0.00144

Gnomad4 ASJ exome

AF:

0.00383

Gnomad4 EAS exome

AF:

0.000446

Gnomad4 SAS exome

AF:

0.00713

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000822

Gnomad4 OTH exome

AF:

0.00186

GnomAD4 genome

AF:

0.000977

AC:

136

AN:

139236

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

AN XY:

67722

show subpopulations

Gnomad4 AFR

AF:

0.000158

Gnomad4 AMR

AF:

0.000907

Gnomad4 ASJ

AF:

0.00387

Gnomad4 EAS

AF:

0.000416

Gnomad4 SAS

AF:

0.00739

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00110

Gnomad4 OTH

AF:

0.000521

Alfa

AF:

0.00169

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 21, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SMPD1: PM4, BS2 -

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

Benign:1

Jan 15, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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