rs3838786
Variant names:
Your query was ambiguous. Multiple possible variants found:
- chr11-6390705-TGCTGGCGCTGGCGCTGGCGCTGGC-T
- chr11-6390705-TGCTGGCGCTGGCGCTGGCGCTGGC-TGCTGGC
- chr11-6390705-TGCTGGCGCTGGCGCTGGCGCTGGC-TGCTGGCGCTGGC
- chr11-6390705-TGCTGGCGCTGGCGCTGGCGCTGGC-TGCTGGCGCTGGCGCTGGC
- chr11-6390705-TGCTGGCGCTGGCGCTGGCGCTGGC-TGCTGGCGCTGGCGCTGGCGCTGGCGCTGGC
- chr11-6390705-TGCTGGCGCTGGCGCTGGCGCTGGC-TGCTGGCGCTGGCGCTGGCGCTGGCGCTGGCGCTGGC
- chr11-6390705-TGCTGGCGCTGGCGCTGGCGCTGGC-TGCTGGCGCTGGCGCTGGCGCTGGCGCTGGCGCTGGCGCTGGC
- chr11-6390705-TGCTGGCGCTGGCGCTGGCGCTGGC-TGCTGGCGCTGGCGCTGGCGCTGGCGCTGGCGCTGGCGCTGGCGCTGGC
- chr11-6390705-TGCTGGCGCTGGCGCTGGCGCTGGC-TGCTGGCGCTGGCGCTGGCGCTGGCGCTGGCGCTGGCGCTGGCGCTGGCGCTGGC
Variant summary
Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM1BP3
The NM_000543.5(SMPD1):c.120_143delGCTGGCGCTGGCGCTGGCGCTGGC(p.Leu41_Ala48del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000326 in 1,594,986 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A40A) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.000048 ( 0 hom., cov: 0)
Exomes 𝑓: 0.000031 ( 0 hom. )
Consequence
SMPD1
NM_000543.5 disruptive_inframe_deletion
NM_000543.5 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.65
Publications
17 publications found
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 Gene-Disease associations (from GenCC):
- acid sphingomyelinase deficiencyInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- Niemann-Pick diseaseInheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health
- Niemann-Pick disease type AInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, PanelApp Australia, G2P
- Niemann-Pick disease type BInheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 1 ACMG points.
PM1
In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 3 benign, 7 uncertain in NM_000543.5
BP3
Nonframeshift variant in repetitive region in NM_000543.5
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000543.5. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SMPD1 | MANE Select | c.120_143delGCTGGCGCTGGCGCTGGCGCTGGC | p.Leu41_Ala48del | disruptive_inframe_deletion | Exon 1 of 6 | NP_000534.3 | |||
| SMPD1 | c.120_143delGCTGGCGCTGGCGCTGGCGCTGGC | p.Leu41_Ala48del | disruptive_inframe_deletion | Exon 1 of 6 | NP_001007594.2 | P17405-4 | |||
| SMPD1 | c.120_143delGCTGGCGCTGGCGCTGGCGCTGGC | p.Leu41_Ala48del | disruptive_inframe_deletion | Exon 1 of 5 | NP_001352064.1 | P17405-2 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SMPD1 | TSL:1 MANE Select | c.120_143delGCTGGCGCTGGCGCTGGCGCTGGC | p.Leu41_Ala48del | disruptive_inframe_deletion | Exon 1 of 6 | ENSP00000340409.4 | P17405-1 | ||
| SMPD1 | TSL:1 | n.120_143delGCTGGCGCTGGCGCTGGCGCTGGC | non_coding_transcript_exon | Exon 1 of 6 | ENSP00000432625.1 | E9PPK6 | |||
| SMPD1 | TSL:1 | n.120_143delGCTGGCGCTGGCGCTGGCGCTGGC | non_coding_transcript_exon | Exon 1 of 5 | ENSP00000435950.1 | G3V1E1 |
Frequencies
GnomAD3 genomes 0.0000475 AC: 7AN: 147228Hom.: 0 Cov.: 0 show subpopulations
GnomAD3 genomes
AF:
AC:
7
AN:
147228
Hom.:
Cov.:
0
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.0000311 AC: 45AN: 1447758Hom.: 0 AF XY: 0.0000347 AC XY: 25AN XY: 720014 show subpopulations
GnomAD4 exome
AF:
AC:
45
AN:
1447758
Hom.:
AF XY:
AC XY:
25
AN XY:
720014
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33148
American (AMR)
AF:
AC:
0
AN:
44336
Ashkenazi Jewish (ASJ)
AF:
AC:
2
AN:
25808
East Asian (EAS)
AF:
AC:
0
AN:
39504
South Asian (SAS)
AF:
AC:
0
AN:
85446
European-Finnish (FIN)
AF:
AC:
0
AN:
51776
Middle Eastern (MID)
AF:
AC:
1
AN:
5692
European-Non Finnish (NFE)
AF:
AC:
40
AN:
1102378
Other (OTH)
AF:
AC:
2
AN:
59670
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.522
Heterozygous variant carriers
0
3
5
8
10
13
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
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>80
Age
GnomAD4 genome 0.0000475 AC: 7AN: 147228Hom.: 0 Cov.: 0 AF XY: 0.0000278 AC XY: 2AN XY: 71866 show subpopulations
GnomAD4 genome
AF:
AC:
7
AN:
147228
Hom.:
Cov.:
0
AF XY:
AC XY:
2
AN XY:
71866
show subpopulations
African (AFR)
AF:
AC:
0
AN:
40092
American (AMR)
AF:
AC:
0
AN:
14846
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3374
East Asian (EAS)
AF:
AC:
0
AN:
5012
South Asian (SAS)
AF:
AC:
0
AN:
4640
European-Finnish (FIN)
AF:
AC:
0
AN:
10138
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
7
AN:
65934
Other (OTH)
AF:
AC:
0
AN:
2020
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.496
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
Hom.:
ClinVar
ClinVar submissions
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
Niemann-Pick disease, type A;C0268243:Niemann-Pick disease, type B (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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