chr10-17709047-T-C

Variant names:

• chr10-17709047-T-C
• rs942775
• NM_003473.4:c.1385+96T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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 -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.

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.1385+96T>C		intron	N/A	NP_003464.1
	STAM	NM_001324282.2		c.1289+96T>C		intron	N/A	NP_001311211.1
	STAM	NM_001324283.2		c.1235+96T>C		intron	N/A	NP_001311212.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAM	ENST00000377524.8	TSL:1 MANE Select	c.1385+96T>C		intron	N/A	ENSP00000366746.3

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

African (AFR) AF: 0.0649 AC: 1874 AN: 28884

American (AMR) AF: 0.111 AC: 3672 AN: 33206

Ashkenazi Jewish (ASJ) AF: 0.0682 AC: 1361 AN: 19960

East Asian (EAS) AF: 0.0426 AC: 1613 AN: 37892

South Asian (SAS) AF: 0.0611 AC: 4293 AN: 70214

European-Finnish (FIN) AF: 0.0888 AC: 4323 AN: 48670

Middle Eastern (MID) AF: 0.0961 AC: 478 AN: 4972

European-Non Finnish (NFE) AF: 0.0924 AC: 91072 AN: 985816

Other (OTH) AF: 0.0867 AC: 4635 AN: 53468

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

African (AFR) AF: 0.0652 AC: 2706 AN: 41528

American (AMR) AF: 0.118 AC: 1798 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0686 AC: 238 AN: 3470

East Asian (EAS) AF: 0.0520 AC: 270 AN: 5190

South Asian (SAS) AF: 0.0699 AC: 337 AN: 4820

European-Finnish (FIN) AF: 0.0849 AC: 901 AN: 10608

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0961 AC: 6536 AN: 68010

Other (OTH) AF: 0.0773 AC: 163 AN: 2110

Alfa AF: 0.0882 Hom.: 161

Bravo AF: 0.0861

Asia WGS AF: 0.0800 AC: 279 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.7
DANN	Benign	0.50
PhyloP100		-0.17
Mutation Taster		=100/0	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: rs942775; hg19: chr10-17751046;