rs942775

Positions:

• chr10-17709047-T-C

Variant summary

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

The NM_003473.4(STAM):​c.1385+96T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0881 in 1,435,320 control chromosomes in the GnomAD database, including 5,876 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 0.086 (599 hom., cov: 32)
  • Exomes 𝑓: 0.088 (5277 hom.)
• Consequence: STAM NM_003473.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165

Genes affected

STAM (HGNC:11357): (signal transducing adaptor molecule) This gene encodes a member of the signal-transducing adaptor molecule family. These proteins mediate downstream signaling of cytokine receptors and also play a role in ER to Golgi trafficking by interacting with the coat protein II complex. The encoded protein also associates with hepatocyte growth factor-regulated substrate to form the endosomal sorting complex required for transport-0 (ESCRT-0), which sorts ubiquitinated membrane proteins to the ESCRT-1 complex for lysosomal degradation. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Feb 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAM	NM_003473.4	c.1385+96T>C		intron_variant		ENST00000377524.8	NP_003464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAM	ENST00000377524.8	c.1385+96T>C		intron_variant		1	NM_003473.4	ENSP00000366746	P1

Frequencies

GnomAD3 genomes AF: 0.0860 AC: 13075 AN: 152120 Hom.: 598 Cov.: 32

Gnomad AFR AF: 0.0652

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.0686

Gnomad EAS AF: 0.0517

Gnomad SAS AF: 0.0701

Gnomad FIN AF: 0.0849

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0961

Gnomad OTH AF: 0.0781

GnomAD4 exome AF: 0.0883 AC: 113321 AN: 1283082 Hom.: 5277 AF XY: 0.0877 AC XY: 55439 AN XY: 632154

Gnomad4 AFR exome AF: 0.0649

Gnomad4 AMR exome AF: 0.111

Gnomad4 ASJ exome AF: 0.0682

Gnomad4 EAS exome AF: 0.0426

Gnomad4 SAS exome AF: 0.0611

Gnomad4 FIN exome AF: 0.0888

Gnomad4 NFE exome AF: 0.0924

Gnomad4 OTH exome AF: 0.0867

GnomAD4 genome AF: 0.0860 AC: 13087 AN: 152238 Hom.: 599 Cov.: 32 AF XY: 0.0856 AC XY: 6374 AN XY: 74440

Gnomad4 AFR AF: 0.0652

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.0686

Gnomad4 EAS AF: 0.0520

Gnomad4 SAS AF: 0.0699

Gnomad4 FIN AF: 0.0849

Gnomad4 NFE AF: 0.0961

Gnomad4 OTH AF: 0.0773

Alfa AF: 0.0887 Hom.: 158

Bravo AF: 0.0861

Asia WGS AF: 0.0800 AC: 279 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.7
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs942775; hg19: chr10-17751046;