Variant chr10-17695245-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_003473.4(STAM):c.728+4A>G variant causes a splice donor 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. 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_donor_region, intron

Scores

Splicing: ADA: 0.7880

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.26

Variant links:

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]

STAM links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 782149.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAM	NM_003473.4 linkuse as main transcript	c.728+4A>G		splice_donor_region_variant, intron_variant		ENST00000377524.8

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
STAM	ENST00000377524.8 linkuse as main transcript	c.728+4A>G	splice_donor_region_variant, intron_variant	1	NM_003473.4	P1	Q92783-1
STAM	ENST00000377500.1 linkuse as main transcript	c.395+4A>G	splice_donor_region_variant, intron_variant	5
STAM	ENST00000494250.1 linkuse as main transcript	n.316+4A>G	splice_donor_region_variant, intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.00736

AC:

1120

AN:

152188

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.00639

AC:

1594

AN:

249606

Hom.:

AF XY:

0.00627

AC XY:

846

AN XY:

134940

show subpopulations

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 SAS exome

AF:

0.0000660

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.:

AF XY:

0.00984

AC XY:

7144

AN XY:

725654

show subpopulations

Gnomad4 AFR exome

AF:

0.00260

Gnomad4 AMR exome

AF:

0.00875

Gnomad4 ASJ exome

AF:

0.00372

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000198

Gnomad4 FIN exome

AF:

0.00249

Gnomad4 NFE exome

AF:

0.0121

Gnomad4 OTH exome

AF:

0.00945

GnomAD4 genome

AF:

0.00735

AC:

1120

AN:

152306

Hom.:

Cov.:

AF XY:

0.00700

AC XY:

521

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00233

Gnomad4 AMR

AF:

0.0128

Gnomad4 ASJ

AF:

0.00749

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00273

Gnomad4 NFE

AF:

0.0106

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.00851

Hom.:

Bravo

AF:

0.00825

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0102

EpiControl

AF:

0.00949

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2022	STAM: BP4, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over