Genetic Variant NSMAF:c.1126-21_1126-12dupTTTTTTTTTT (chr8-58601546-G-GAAAAAAAAAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_003580.4(NSMAF):c.1126-21_1126-12dupTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000037 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000028 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NSMAF
NM_003580.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.861

Publications

1 publications found

Variant links:

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]

NSMAF links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003580.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NSMAF	NM_003580.4	MANE Select	c.1126-21_1126-12dupTTTTTTTTTT	intron	N/A	NP_003571.2
NSMAF	NM_001144772.1		c.1219-21_1219-12dupTTTTTTTTTT	intron	N/A	NP_001138244.1	Q92636-2
NSMAF	NM_001413006.1		c.1195-21_1195-12dupTTTTTTTTTT	intron	N/A	NP_001399935.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NSMAF	ENST00000038176.8	TSL:1 MANE Select	c.1126-12_1126-11insTTTTTTTTTT	intron	N/A	ENSP00000038176.3	Q92636-1
NSMAF	ENST00000427130.7	TSL:2	c.1219-12_1219-11insTTTTTTTTTT	intron	N/A	ENSP00000411012.2	Q92636-2
NSMAF	ENST00000958102.1		c.1147-12_1147-11insTTTTTTTTTT	intron	N/A	ENSP00000628161.1

Frequencies

GnomAD3 genomes

AF:

0.0000369

AC:

AN:

135474

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000726

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000432

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000159

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000283

AC:

AN:

1308502

Hom.:

Cov.:

AF XY:

0.0000310

AC XY:

AN XY:

645392

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000360

AC:

AN:

27764

American (AMR)

AF:

0.00

AC:

AN:

21786

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20334

East Asian (EAS)

AF:

0.000144

AC:

AN:

34606

South Asian (SAS)

AF:

0.000156

AC:

AN:

64192

European-Finnish (FIN)

AF:

0.0000240

AC:

AN:

41706

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4578

European-Non Finnish (NFE)

AF:

0.0000183

AC:

AN:

1039426

Other (OTH)

AF:

0.0000185

AC:

AN:

54110

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.316

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000369

AC:

AN:

135492

Hom.:

Cov.:

AF XY:

0.0000460

AC XY:

AN XY:

65194

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

36886

American (AMR)

AF:

0.0000726

AC:

AN:

13780

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3312

East Asian (EAS)

AF:

0.00

AC:

AN:

4502

South Asian (SAS)

AF:

0.00

AC:

AN:

4296

European-Finnish (FIN)

AF:

0.000432

AC:

AN:

6946

Middle Eastern (MID)

AF:

0.00

AC:

AN:

258

European-Non Finnish (NFE)

AF:

0.0000159

AC:

AN:

62824

Other (OTH)

AF:

0.00

AC:

AN:

1874

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.86

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

8-58601546-GAAAAA-GAAAAAAAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over