NM_003473.4:c.123T>C

Variant names:

• chr10-17660546-T-C
• rs41289333
• NM_003473.4:c.123T>C

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_003473.4(STAM):​c.123T>C​(p.Thr41Thr) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 1,588,300 control chromosomes in the GnomAD database, including 135 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0083 (11 hom., cov: 32)
  • Exomes 𝑓: 0.012 (124 hom.)
• Consequence: STAM NM_003473.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.00005715
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.53
• 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 10-17660546-T-C is Benign according to our data. Variant chr10-17660546-T-C is described in ClinVar as Benign. ClinVar VariationId is 778035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.0115 (16532/1435990) while in subpopulation MID AF = 0.0347 (197/5672). AF 95% confidence interval is 0.0308. There are 124 homozygotes in GnomAdExome4. There are 8479 alleles in the male GnomAdExome4 subpopulation. Median coverage is 29. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAM	NM_003473.4	MANE Select	c.123T>C	p.Thr41Thr	splice_region synonymous	Exon 2 of 14	NP_003464.1	Q92783-1
	STAM	NM_001324284.2		c.-132T>C		splice_region	Exon 2 of 15	NP_001311213.1
	STAM	NM_001324285.2		c.-140T>C		splice_region	Exon 2 of 15	NP_001311214.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAM	ENST00000377524.8	TSL:1 MANE Select	c.123T>C	p.Thr41Thr	splice_region synonymous	Exon 2 of 14	ENSP00000366746.3	Q92783-1
	STAM	ENST00000892730.1		c.123T>C	p.Thr41Thr	splice_region synonymous	Exon 2 of 14	ENSP00000562789.1
	STAM	ENST00000945545.1		c.123T>C	p.Thr41Thr	splice_region synonymous	Exon 2 of 14	ENSP00000615604.1

Frequencies

GnomAD3 genomes AF: 0.00826 AC: 1257 AN: 152192 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.00236

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0104

Gnomad ASJ AF: 0.0205

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0160

Gnomad FIN AF: 0.00254

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0116

Gnomad OTH AF: 0.0129

GnomAD2 exomes AF: 0.0105 AC: 2221 AN: 211064 AF XY: 0.0115

Gnomad AFR exome AF: 0.00173

Gnomad AMR exome AF: 0.00892

Gnomad ASJ exome AF: 0.0230

Gnomad EAS exome AF: 0.000136

Gnomad FIN exome AF: 0.00219

Gnomad NFE exome AF: 0.0122

Gnomad OTH exome AF: 0.0122

GnomAD4 exome AF: 0.0115 AC: 16532 AN: 1435990 Hom.: 124 Cov.: 29 AF XY: 0.0119 AC XY: 8479 AN XY: 714360

African (AFR) AF: 0.00292 AC: 93 AN: 31886

American (AMR) AF: 0.00750 AC: 309 AN: 41196

Ashkenazi Jewish (ASJ) AF: 0.0176 AC: 450 AN: 25504

East Asian (EAS) AF: 0.000131 AC: 5 AN: 38082

South Asian (SAS) AF: 0.0170 AC: 1409 AN: 82772

European-Finnish (FIN) AF: 0.00274 AC: 145 AN: 52868

Middle Eastern (MID) AF: 0.0347 AC: 197 AN: 5672

European-Non Finnish (NFE) AF: 0.0120 AC: 13205 AN: 1098810

Other (OTH) AF: 0.0121 AC: 719 AN: 59200

GnomAD4 genome AF: 0.00825 AC: 1257 AN: 152310 Hom.: 11 Cov.: 32 AF XY: 0.00808 AC XY: 602 AN XY: 74470

African (AFR) AF: 0.00236 AC: 98 AN: 41576

American (AMR) AF: 0.0104 AC: 159 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0205 AC: 71 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.0160 AC: 77 AN: 4820

European-Finnish (FIN) AF: 0.00254 AC: 27 AN: 10622

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0116 AC: 789 AN: 68020

Other (OTH) AF: 0.0128 AC: 27 AN: 2112

Alfa AF: 0.0103 Hom.: 1

Bravo AF: 0.00818

Asia WGS AF: 0.00664 AC: 24 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	14
DANN	Benign	0.77
PhyloP100		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=277/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000057
dbscSNV1_RF	Benign	0.0040
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: rs41289333; hg19: chr10-17702545;