rs1937348

Variant names:

• chr10-17648683-T-C
• rs1937348
• NM_003473.4:c.40+4304T>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.40+4304T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 152,044 control chromosomes in the GnomAD database, including 33,347 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 0.64 (33347 hom., cov: 31)
• Consequence: STAM NM_003473.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.229
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.873 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAM	NM_003473.4	c.40+4304T>C		intron_variant	Intron 1 of 13	ENST00000377524.8	NP_003464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAM	ENST00000377524.8	c.40+4304T>C		intron_variant	Intron 1 of 13	1	NM_003473.4	ENSP00000366746.3
STAM	ENST00000377500.1	c.-37+4304T>C		intron_variant	Intron 1 of 5	5		ENSP00000366721.1
STAM	ENST00000445846.1	n.40+4304T>C		intron_variant	Intron 1 of 6	4		ENSP00000400025.1

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97791 AN: 151926 Hom.: 33275 Cov.: 31

Gnomad AFR AF: 0.880

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.656

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.649

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.644 AC: 97923 AN: 152044 Hom.: 33347 Cov.: 31 AF XY: 0.638 AC XY: 47424 AN XY: 74310

African (AFR) AF: 0.880 AC: 36537 AN: 41500

American (AMR) AF: 0.656 AC: 10019 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.589 AC: 2044 AN: 3468

East Asian (EAS) AF: 0.526 AC: 2714 AN: 5158

South Asian (SAS) AF: 0.511 AC: 2460 AN: 4816

European-Finnish (FIN) AF: 0.471 AC: 4977 AN: 10572

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.547 AC: 37163 AN: 67936

Other (OTH) AF: 0.653 AC: 1381 AN: 2114

Alfa AF: 0.583 Hom.: 49778

Bravo AF: 0.668

Asia WGS AF: 0.577 AC: 2009 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.54
PhyloP100		-0.23
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: rs1937348; hg19: chr10-17690682;