dbSNP rs33942423: NSMAF:c.1126-16_1126-12delTTTTT (chr8-58601546-GAAAAA-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003580.4(NSMAF):c.1126-16_1126-12delTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000153 in 1,308,550 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 0)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

NSMAF
NM_003580.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.07

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NSMAF	NM_003580.4 link	c.1126-16_1126-12delTTTTT		intron_variant	Intron 14 of 30	ENST00000038176.8	NP_003571.2	Q92636-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
NSMAF	ENST00000038176.8 link	c.1126-16_1126-12delTTTTT	intron_variant	Intron 14 of 30	1	NM_003580.4	ENSP00000038176.3	Q92636-1
NSMAF	ENST00000427130.7 link	c.1219-16_1219-12delTTTTT	intron_variant	Intron 14 of 30	2		ENSP00000411012.2	Q92636-2
NSMAF	ENST00000519858.1 link	n.665-16_665-12delTTTTT	intron_variant	Intron 7 of 8	3
NSMAF	ENST00000649465.1 link	n.1252-16_1252-12delTTTTT	intron_variant	Intron 16 of 32			ENSP00000498107.1	E5RGU2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000153

AC:

AN:

1308550

Hom.:

AF XY:

0.00000155

AC XY:

AN XY:

645422

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27764

American (AMR)

AF:

0.00

AC:

AN:

21790

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20340

East Asian (EAS)

AF:

0.00

AC:

AN:

34608

South Asian (SAS)

AF:

0.00

AC:

AN:

64204

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41706

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4578

European-Non Finnish (NFE)

AF:

0.00000192

AC:

AN:

1039446

Other (OTH)

AF:

0.00

AC:

AN:

54114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.1

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over