8-58596021-C-T

Position:

• chr8-58596021-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000038176.8(NSMAF):​c.1793-362G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.028 in 204,394 control chromosomes in the GnomAD database, including 164 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.030 (129 hom., cov: 32)
  • Exomes 𝑓: 0.022 (35 hom.)
• Consequence: NSMAF ENST00000038176.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.811

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NSMAF	NM_003580.4	c.1793-362G>A		intron_variant		ENST00000038176.8	NP_003571.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NSMAF	ENST00000038176.8	c.1793-362G>A		intron_variant		1	NM_003580.4	ENSP00000038176	P1
NSMAF	ENST00000427130.6	c.1886-362G>A		intron_variant		2		ENSP00000411012
NSMAF	ENST00000649465.1	c.*1932-362G>A		intron_variant, NMD_transcript_variant				ENSP00000498107
NSMAF	ENST00000523106.5	n.457-362G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0302 AC: 4591 AN: 152086 Hom.: 130 Cov.: 32

Gnomad AFR AF: 0.0624

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0138

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.0792

Gnomad SAS AF: 0.0526

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0148

Gnomad OTH AF: 0.0263

GnomAD4 exome AF: 0.0219 AC: 1141 AN: 52190 Hom.: 35 AF XY: 0.0249 AC XY: 731 AN XY: 29358

Gnomad4 AFR exome AF: 0.0531

Gnomad4 AMR exome AF: 0.00852

Gnomad4 ASJ exome AF: 0.00917

Gnomad4 EAS exome AF: 0.0641

Gnomad4 SAS exome AF: 0.0454

Gnomad4 FIN exome AF: 0.00280

Gnomad4 NFE exome AF: 0.0113

Gnomad4 OTH exome AF: 0.0154

GnomAD4 genome AF: 0.0302 AC: 4591 AN: 152204 Hom.: 129 Cov.: 32 AF XY: 0.0298 AC XY: 2219 AN XY: 74404

Gnomad4 AFR AF: 0.0624

Gnomad4 AMR AF: 0.0138

Gnomad4 ASJ AF: 0.0130

Gnomad4 EAS AF: 0.0788

Gnomad4 SAS AF: 0.0523

Gnomad4 FIN AF: 0.00160

Gnomad4 NFE AF: 0.0148

Gnomad4 OTH AF: 0.0260

Alfa AF: 0.0187 Hom.: 52

Bravo AF: 0.0319

Asia WGS AF: 0.0430 AC: 148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.1
DANN	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs11994937; hg19: chr8-59508580;