10-17714597-T-C

Variant names:

• chr10-17714597-T-C
• rs12221
• NM_003473.4:c.1440T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003473.4(STAM):​c.1440T>C​(p.Tyr480Tyr) 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
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003473.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAM	NM_003473.4	MANE Select	c.1440T>C	p.Tyr480Tyr	synonymous	Exon 14 of 14	NP_003464.1
	STAM	NM_001324282.2		c.1344T>C	p.Tyr448Tyr	synonymous	Exon 13 of 13	NP_001311211.1
	STAM	NM_001324283.2		c.1290T>C	p.Tyr430Tyr	synonymous	Exon 13 of 13	NP_001311212.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAM	ENST00000377524.8	TSL:1 MANE Select	c.1440T>C	p.Tyr480Tyr	synonymous	Exon 14 of 14	ENSP00000366746.3

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

GnomAD2 exomes AF: 0.193 AC: 48543 AN: 251368 AF XY: 0.194

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 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

African (AFR) AF: 0.105 AC: 3527 AN: 33478

American (AMR) AF: 0.112 AC: 5029 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 7044 AN: 26136

East Asian (EAS) AF: 0.204 AC: 8087 AN: 39700

South Asian (SAS) AF: 0.138 AC: 11929 AN: 86258

European-Finnish (FIN) AF: 0.254 AC: 13581 AN: 53410

Middle Eastern (MID) AF: 0.251 AC: 1449 AN: 5768

European-Non Finnish (NFE) AF: 0.220 AC: 245125 AN: 1111974

Other (OTH) AF: 0.212 AC: 12833 AN: 60396

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

African (AFR) AF: 0.104 AC: 4333 AN: 41512

American (AMR) AF: 0.147 AC: 2252 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 995 AN: 3472

East Asian (EAS) AF: 0.200 AC: 1034 AN: 5174

South Asian (SAS) AF: 0.131 AC: 631 AN: 4818

European-Finnish (FIN) AF: 0.257 AC: 2715 AN: 10580

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15191 AN: 67994

Other (OTH) AF: 0.207 AC: 438 AN: 2114

Alfa AF: 0.212 Hom.: 15558

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.11
DANN	Benign	0.31
PhyloP100		-0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

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