Genetic Variant NSMAF:c.1126-14_1126-12dupTTT (chr8-58601546-G-GAAA) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_003580.4(NSMAF):c.1126-14_1126-12dupTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.43 ( 12890 hom., cov: 0)

Exomes 𝑓: 0.32 ( 6738 hom. )

Failed GnomAD Quality Control

Consequence

NSMAF
NM_003580.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.861

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 made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 8-58601546-G-GAAA is Benign according to our data. Variant chr8-58601546-G-GAAA is described in ClinVar as [Benign]. Clinvar id is 403262.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NSMAF	NM_003580.4 link	c.1126-14_1126-12dupTTT		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.1126-12_1126-11insTTT	intron_variant	Intron 14 of 30	1	NM_003580.4	ENSP00000038176.3	Q92636-1
NSMAF	ENST00000427130.6 link	c.1219-12_1219-11insTTT	intron_variant	Intron 14 of 30	2		ENSP00000411012.2	Q92636-2
NSMAF	ENST00000519858.1 link	n.665-12_665-11insTTT	intron_variant	Intron 7 of 8	3
NSMAF	ENST00000649465.1 link	n.1252-12_1252-11insTTT	intron_variant	Intron 16 of 32			ENSP00000498107.1	E5RGU2

Frequencies

GnomAD3 genomes

AF:

0.431

AC:

58271

AN:

135098

Hom.:

12886

Cov.:

show subpopulations

Gnomad AFR

AF:

0.253

Gnomad AMI

AF:

0.453

Gnomad AMR

AF:

0.569

Gnomad ASJ

AF:

0.548

Gnomad EAS

AF:

0.512

Gnomad SAS

AF:

0.494

Gnomad FIN

AF:

0.373

Gnomad MID

AF:

0.525

Gnomad NFE

AF:

0.494

Gnomad OTH

AF:

0.462

GnomAD3 exomes

AF:

0.222

AC:

22497

AN:

101380

Hom.:

2663

AF XY:

0.217

AC XY:

12009

AN XY:

55258

show subpopulations

Gnomad AFR exome

AF:

0.153

Gnomad AMR exome

AF:

0.299

Gnomad ASJ exome

AF:

0.229

Gnomad EAS exome

AF:

0.244

Gnomad SAS exome

AF:

0.208

Gnomad FIN exome

AF:

0.161

Gnomad NFE exome

AF:

0.226

Gnomad OTH exome

AF:

0.245

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.322

AC:

392723

AN:

1219316

Hom.:

6738

Cov.:

AF XY:

0.319

AC XY:

192245

AN XY:

602170

show subpopulations

Gnomad4 AFR exome

AF:

0.207

Gnomad4 AMR exome

AF:

0.330

Gnomad4 ASJ exome

AF:

0.337

Gnomad4 EAS exome

AF:

0.294

Gnomad4 SAS exome

AF:

0.289

Gnomad4 FIN exome

AF:

0.230

Gnomad4 NFE exome

AF:

0.332

Gnomad4 OTH exome

AF:

0.320

GnomAD4 genome

AF:

0.431

AC:

58270

AN:

135116

Hom.:

12890

Cov.:

AF XY:

0.429

AC XY:

27906

AN XY:

65000

show subpopulations

Gnomad4 AFR

AF:

0.253

Gnomad4 AMR

AF:

0.570

Gnomad4 ASJ

AF:

0.548

Gnomad4 EAS

AF:

0.512

Gnomad4 SAS

AF:

0.493

Gnomad4 FIN

AF:

0.373

Gnomad4 NFE

AF:

0.494

Gnomad4 OTH

AF:

0.463

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

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.

8-58601546-GAAAAA-GAAAAAAAA

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