NM_003580.4:c.1126-13_1126-12dupTT
Variant summary
Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1
The NM_003580.4(NSMAF):c.1126-13_1126-12dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0981 in 1,406,474 control chromosomes in the GnomAD database, including 3,168 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.13 ( 1904 hom., cov: 0)
Exomes 𝑓: 0.094 ( 1264 hom. )
Consequence
NSMAF
NM_003580.4 intron
NM_003580.4 intron
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.861
Publications
1 publications found
Genes affected
NSMAF (HGNC:8017): (neutral sphingomyelinase activation associated factor) This gene encodes a WD-repeat protein that binds the cytoplasmic sphingomyelinase activation domain of the 55kD tumor necrosis factor receptor. This protein is required for TNF-mediated activation of neutral sphingomyelinase and may play a role in regulating TNF-induced cellular responses such as inflammation. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Jan 2009]
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ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -8 ACMG points.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NSMAF | ENST00000038176.8 | c.1126-13_1126-12dupTT | intron_variant | Intron 14 of 30 | 1 | NM_003580.4 | ENSP00000038176.3 | |||
NSMAF | ENST00000427130.7 | c.1219-13_1219-12dupTT | intron_variant | Intron 14 of 30 | 2 | ENSP00000411012.2 | ||||
NSMAF | ENST00000519858.1 | n.665-13_665-12dupTT | intron_variant | Intron 7 of 8 | 3 | |||||
NSMAF | ENST00000649465.1 | n.*1252-13_*1252-12dupTT | intron_variant | Intron 16 of 32 | ENSP00000498107.1 |
Frequencies
GnomAD3 genomes AF: 0.133 AC: 18012AN: 135374Hom.: 1903 Cov.: 0 show subpopulations
GnomAD3 genomes
AF:
AC:
18012
AN:
135374
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:
GnomAD2 exomes AF: 0.121 AC: 12276AN: 101380 AF XY: 0.118 show subpopulations
GnomAD2 exomes
AF:
AC:
12276
AN:
101380
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0943 AC: 119894AN: 1271080Hom.: 1264 Cov.: 32 AF XY: 0.0937 AC XY: 58769AN XY: 627052 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
119894
AN:
1271080
Hom.:
Cov.:
32
AF XY:
AC XY:
58769
AN XY:
627052
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
6885
AN:
26894
American (AMR)
AF:
AC:
2312
AN:
21190
Ashkenazi Jewish (ASJ)
AF:
AC:
2305
AN:
19692
East Asian (EAS)
AF:
AC:
1298
AN:
33612
South Asian (SAS)
AF:
AC:
6056
AN:
62750
European-Finnish (FIN)
AF:
AC:
3676
AN:
40768
Middle Eastern (MID)
AF:
AC:
462
AN:
4444
European-Non Finnish (NFE)
AF:
AC:
91626
AN:
1009198
Other (OTH)
AF:
AC:
5274
AN:
52532
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.351
Heterozygous variant carriers
0
5663
11327
16990
22654
28317
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Exome Hom
Variant carriers
0
3648
7296
10944
14592
18240
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome AF: 0.133 AC: 18026AN: 135394Hom.: 1904 Cov.: 0 AF XY: 0.131 AC XY: 8552AN XY: 65142 show subpopulations
GnomAD4 genome
AF:
AC:
18026
AN:
135394
Hom.:
Cov.:
0
AF XY:
AC XY:
8552
AN XY:
65142
show subpopulations
African (AFR)
AF:
AC:
10877
AN:
36818
American (AMR)
AF:
AC:
1037
AN:
13774
Ashkenazi Jewish (ASJ)
AF:
AC:
338
AN:
3310
East Asian (EAS)
AF:
AC:
30
AN:
4504
South Asian (SAS)
AF:
AC:
317
AN:
4292
European-Finnish (FIN)
AF:
AC:
460
AN:
6940
Middle Eastern (MID)
AF:
AC:
24
AN:
258
European-Non Finnish (NFE)
AF:
AC:
4706
AN:
62810
Other (OTH)
AF:
AC:
207
AN:
1874
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.498
Heterozygous variant carriers
0
651
1302
1952
2603
3254
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Genome Hom
Variant carriers
0
176
352
528
704
880
<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
Not reported inComputational 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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