rs72782571

Variant names:

• chr10-17695245-A-G
• rs72782571
• NM_003473.4:c.728+4A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_003473.4(STAM):​c.728+4A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00986 in 1,611,386 control chromosomes in the GnomAD database, including 108 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 0.0074 (7 hom., cov: 33)
  • Exomes 𝑓: 0.010 (101 hom.)
• Consequence: STAM NM_003473.4 splice_region, intron
• Scores: Splicing: ADA: 0.7880
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.26
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 10-17695245-A-G is Benign according to our data. Variant chr10-17695245-A-G is described in ClinVar as Benign. ClinVar VariationId is 782149.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 7 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.728+4A>G		splice_region intron	N/A	NP_003464.1	Q92783-1
	STAM	NM_001324282.2		c.632+4A>G		splice_region intron	N/A	NP_001311211.1
	STAM	NM_001324283.2		c.578+4A>G		splice_region intron	N/A	NP_001311212.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAM	ENST00000377524.8	TSL:1 MANE Select	c.728+4A>G		splice_region intron	N/A	ENSP00000366746.3	Q92783-1
	STAM	ENST00000892730.1		c.728+4A>G		splice_region intron	N/A	ENSP00000562789.1
	STAM	ENST00000945545.1		c.728+4A>G		splice_region intron	N/A	ENSP00000615604.1

Frequencies

GnomAD3 genomes AF: 0.00736 AC: 1120 AN: 152188 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.00234

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0128

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00273

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0106

Gnomad OTH AF: 0.0144

GnomAD2 exomes AF: 0.00639 AC: 1594 AN: 249606 AF XY: 0.00627

Gnomad AFR exome AF: 0.00303

Gnomad AMR exome AF: 0.00771

Gnomad ASJ exome AF: 0.00378

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00277

Gnomad NFE exome AF: 0.00990

Gnomad OTH exome AF: 0.0102

GnomAD4 exome AF: 0.0101 AC: 14769 AN: 1459080 Hom.: 101 Cov.: 29 AF XY: 0.00984 AC XY: 7144 AN XY: 725654

African (AFR) AF: 0.00260 AC: 87 AN: 33400

American (AMR) AF: 0.00875 AC: 390 AN: 44562

Ashkenazi Jewish (ASJ) AF: 0.00372 AC: 97 AN: 26084

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39624

South Asian (SAS) AF: 0.000198 AC: 17 AN: 85958

European-Finnish (FIN) AF: 0.00249 AC: 132 AN: 53048

Middle Eastern (MID) AF: 0.000869 AC: 5 AN: 5756

European-Non Finnish (NFE) AF: 0.0121 AC: 13470 AN: 1110348

Other (OTH) AF: 0.00945 AC: 570 AN: 60300

GnomAD4 genome AF: 0.00735 AC: 1120 AN: 152306 Hom.: 7 Cov.: 33 AF XY: 0.00700 AC XY: 521 AN XY: 74478

African (AFR) AF: 0.00233 AC: 97 AN: 41562

American (AMR) AF: 0.0128 AC: 196 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00749 AC: 26 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.00273 AC: 29 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0106 AC: 724 AN: 68030

Other (OTH) AF: 0.0142 AC: 30 AN: 2112

Alfa AF: 0.00871 Hom.: 4

Bravo AF: 0.00825

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0102

EpiControl AF: 0.00949

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	-0.36
CADD	Benign	20
DANN	Benign	0.90
PhyloP100		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.79
dbscSNV1_RF	Benign	0.41
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: rs72782571; hg19: chr10-17737244;