chr10-17660544-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_003473.4(STAM):c.121A>C(p.Thr41Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000225 in 1,597,446 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T41T) has been classified as Benign.
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000023 ( 0 hom. )
Consequence
STAM
NM_003473.4 missense
NM_003473.4 missense
Scores
7
12
Clinical Significance
Conservation
PhyloP100: 6.99
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STAM | NM_003473.4 | c.121A>C | p.Thr41Pro | missense_variant | 2/14 | ENST00000377524.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STAM | ENST00000377524.8 | c.121A>C | p.Thr41Pro | missense_variant | 2/14 | 1 | NM_003473.4 | P1 | |
STAM | ENST00000377500.1 | c.-37+16165A>C | intron_variant | 5 | |||||
STAM | ENST00000445846.1 | c.121A>C | p.Thr41Pro | missense_variant, NMD_transcript_variant | 2/7 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152172Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000126 AC: 3AN: 238772Hom.: 0 AF XY: 0.00000772 AC XY: 1AN XY: 129460
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GnomAD4 exome AF: 0.0000228 AC: 33AN: 1445274Hom.: 0 Cov.: 29 AF XY: 0.0000222 AC XY: 16AN XY: 719122
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152172Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74340
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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 | Oct 05, 2023 | The c.121A>C (p.T41P) alteration is located in exon 2 (coding exon 2) of the STAM gene. This alteration results from a A to C substitution at nucleotide position 121, causing the threonine (T) at amino acid position 41 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Uncertain
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at