8-58601546-GAAAAA-GAAAAAAAAAA

Variant names:

• chr8-58601546-G-GAAAAA
• rs33942423
• NM_003580.4:c.1126-16_1126-12dupTTTTT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_003580.4(NSMAF):​c.1126-16_1126-12dupTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00333 in 1,436,226 control chromosomes in the GnomAD database, including 13 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000081 (1 hom., cov: 0)
  • Exomes 𝑓: 0.0037 (12 hom.)
• Consequence: NSMAF NM_003580.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.861

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 12 AR gene

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NSMAF	ENST00000038176.8	c.1126-12_1126-11insTTTTT		intron_variant	Intron 14 of 30	1	NM_003580.4	ENSP00000038176.3
NSMAF	ENST00000427130.6	c.1219-12_1219-11insTTTTT		intron_variant	Intron 14 of 30	2		ENSP00000411012.2
NSMAF	ENST00000519858.1	n.665-12_665-11insTTTTT		intron_variant	Intron 7 of 8	3
NSMAF	ENST00000649465.1	n.*1252-12_*1252-11insTTTTT		intron_variant	Intron 16 of 32			ENSP00000498107.1

Frequencies

GnomAD3 genomes AF: 0.0000812 AC: 11 AN: 135474 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.0000272

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000159

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00810 AC: 821 AN: 101380 Hom.: 24 AF XY: 0.00771 AC XY: 426 AN XY: 55258

Gnomad AFR exome AF: 0.00329

Gnomad AMR exome AF: 0.0121

Gnomad ASJ exome AF: 0.00776

Gnomad EAS exome AF: 0.00962

Gnomad SAS exome AF: 0.00958

Gnomad FIN exome AF: 0.00265

Gnomad NFE exome AF: 0.00844

Gnomad OTH exome AF: 0.00994

GnomAD4 exome AF: 0.00367 AC: 4773 AN: 1300752 Hom.: 12 Cov.: 32 AF XY: 0.00387 AC XY: 2482 AN XY: 641440

Gnomad4 AFR exome AF: 0.00141

Gnomad4 AMR exome AF: 0.00782

Gnomad4 ASJ exome AF: 0.00639

Gnomad4 EAS exome AF: 0.00311

Gnomad4 SAS exome AF: 0.0108

Gnomad4 FIN exome AF: 0.00243

Gnomad4 NFE exome AF: 0.00319

Gnomad4 OTH exome AF: 0.00422

GnomAD4 genome AF: 0.0000812 AC: 11 AN: 135474 Hom.: 1 Cov.: 0 AF XY: 0.0000614 AC XY: 4 AN XY: 65152

Gnomad4 AFR AF: 0.0000272

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000159

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs33942423; hg19: chr8-59514105;