Variant rs775568984 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_000543.5(SMPD1):c.108_109insGCG(p.Val36_Leu37insAla) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. V36V) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0053 ( 5 hom., cov: 0)

Exomes 𝑓: 0.0048 ( 106 hom. )

Failed GnomAD Quality Control

Consequence

SMPD1
NM_000543.5 inframe_insertion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.158

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 -16 ACMG points.

BP6

Variant 11-6390705-T-TGGC is Benign according to our data. Variant chr11-6390705-T-TGGC is described in ClinVar as [Likely_benign]. Clinvar id is 529235.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00526 (775/147350) while in subpopulation SAS AF= 0.0345 (160/4642). AF 95% confidence interval is 0.0301. There are 5 homozygotes in gnomad4. There are 455 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMPD1	NM_000543.5 linkuse as main transcript	c.108_109insGCG	p.Val36_Leu37insAla	inframe_insertion	1/6	ENST00000342245.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMPD1	ENST00000342245.9 linkuse as main transcript	c.108_109insGCG	p.Val36_Leu37insAla	inframe_insertion	1/6	1	NM_000543.5	P3	P17405-1

Frequencies

GnomAD3 genomes

AF:

0.00528

AC:

777

AN:

147224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00613

Gnomad ASJ

AF:

0.00415

Gnomad EAS

AF:

0.00878

Gnomad SAS

AF:

0.0347

Gnomad FIN

AF:

0.0179

Gnomad MID

AF:

0.0204

Gnomad NFE

AF:

0.00244

Gnomad OTH

AF:

0.00149

GnomAD3 exomes

AF:

0.00721

AC:

1724

AN:

238972

Hom.:

AF XY:

0.00793

AC XY:

1036

AN XY:

130606

show subpopulations

Gnomad AFR exome

AF:

0.00240

Gnomad AMR exome

AF:

0.00630

Gnomad ASJ exome

AF:

0.00602

Gnomad EAS exome

AF:

0.00595

Gnomad SAS exome

AF:

0.0274

Gnomad FIN exome

AF:

0.0117

Gnomad NFE exome

AF:

0.00200

Gnomad OTH exome

AF:

0.00568

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00478

AC:

6924

AN:

1447752

Hom.:

106

Cov.:

AF XY:

0.00546

AC XY:

3931

AN XY:

720008

show subpopulations

Gnomad4 AFR exome

AF:

0.00302

Gnomad4 AMR exome

AF:

0.00701

Gnomad4 ASJ exome

AF:

0.00527

Gnomad4 EAS exome

AF:

0.00694

Gnomad4 SAS exome

AF:

0.0294

Gnomad4 FIN exome

AF:

0.0151

Gnomad4 NFE exome

AF:

0.00220

Gnomad4 OTH exome

AF:

0.00593

GnomAD4 genome

AF:

0.00526

AC:

775

AN:

147350

Hom.:

Cov.:

AF XY:

0.00632

AC XY:

455

AN XY:

71996

show subpopulations

Gnomad4 AFR

AF:

0.00288

Gnomad4 AMR

AF:

0.00612

Gnomad4 ASJ

AF:

0.00415

Gnomad4 EAS

AF:

0.00859

Gnomad4 SAS

AF:

0.0345

Gnomad4 FIN

AF:

0.0179

Gnomad4 NFE

AF:

0.00244

Gnomad4 OTH

AF:

0.00147

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital

Feb 02, 2020

- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Oct 11, 2023

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 13, 2020

See Variant Classification Assertion Criteria. -

Niemann-Pick disease, type A

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Aug 25, 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