rs12221

chr10-17714597-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003473.4(STAM):c.1440T>C(p.Tyr480=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 1,613,996 control chromosomes in the GnomAD database, including 36,514 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 0.18 (2828 hom., cov: 31)
  • Exomes 𝑓: 0.21 (33686 hom.)
• Consequence: STAM NM_003473.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.730

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP7: Synonymous conserved (PhyloP=-0.73 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAM	NM_003473.4	c.1440T>C	p.Tyr480=	synonymous_variant	14/14	ENST00000377524.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAM	ENST00000377524.8	c.1440T>C	p.Tyr480=	synonymous_variant	14/14	1	NM_003473.4	P1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27772 AN: 152034 Hom.: 2824 Cov.: 31

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.203

GnomAD3 exomes AF: 0.193 AC: 48543 AN: 251368 Hom.: 5165 AF XY: 0.194 AC XY: 26379 AN XY: 135860

Gnomad AFR exome AF: 0.106

Gnomad AMR exome AF: 0.107

Gnomad ASJ exome AF: 0.268

Gnomad EAS exome AF: 0.215

Gnomad SAS exome AF: 0.133

Gnomad FIN exome AF: 0.259

Gnomad NFE exome AF: 0.224

Gnomad OTH exome AF: 0.209

GnomAD4 exome AF: 0.211 AC: 308604 AN: 1461844 Hom.: 33686 Cov.: 33 AF XY: 0.209 AC XY: 152225 AN XY: 727216

Gnomad4 AFR exome AF: 0.105

Gnomad4 AMR exome AF: 0.112

Gnomad4 ASJ exome AF: 0.270

Gnomad4 EAS exome AF: 0.204

Gnomad4 SAS exome AF: 0.138

Gnomad4 FIN exome AF: 0.254

Gnomad4 NFE exome AF: 0.220

Gnomad4 OTH exome AF: 0.212

GnomAD4 genome AF: 0.183 AC: 27783 AN: 152152 Hom.: 2828 Cov.: 31 AF XY: 0.182 AC XY: 13558 AN XY: 74360

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.200

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.207

Alfa AF: 0.218 Hom.: 7742

Bravo AF: 0.173

Asia WGS AF: 0.162 AC: 564 AN: 3478

EpiCase AF: 0.230

EpiControl AF: 0.229

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
Cadd	Benign	0.11
Dann	Benign	0.31
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs12221; hg19: chr10-17756596; COSMIC: COSV66351213;