Variant 10-17693277-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003473.4(STAM):c.500T>A(p.Val167Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,668 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

STAM
NM_003473.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.950

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13382316).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAM	NM_003473.4 linkuse as main transcript	c.500T>A	p.Val167Glu	missense_variant	6/14	ENST00000377524.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAM	ENST00000377524.8 linkuse as main transcript	c.500T>A	p.Val167Glu	missense_variant	6/14	1	NM_003473.4	P1	Q92783-1
STAM	ENST00000377500.1 linkuse as main transcript	c.167T>A	p.Val56Glu	missense_variant	3/6	5
STAM	ENST00000445846.1 linkuse as main transcript	c.*475T>A		3_prime_UTR_variant, NMD_transcript_variant	7/7	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460668

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726648

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 28, 2023

The c.500T>A (p.V167E) alteration is located in exon 6 (coding exon 6) of the STAM gene. This alteration results from a T to A substitution at nucleotide position 500, causing the valine (V) at amino acid position 167 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.083

BayesDel_noAF

Benign

-0.36

Cadd

Benign

Dann

Benign

0.96

DEOGEN2

Benign

0.35

T;T

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.47

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.0099

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

N;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-2.4

N;.

REVEL

Benign

0.14

Sift

Uncertain

0.018

D;.

Sift4G

Uncertain

0.045

D;T

Polyphen

0.058

B;.

Vest4

0.49

MutPred

0.25

Loss of methylation at K170 (P = 0.0744);.;

MVP

0.41

MPC

0.17

ClinPred

0.41

GERP RS

-0.47

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.43

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over