rs781788116

Variant names:

• chr10-17695090-A-C
• rs781788116
• NM_003473.4:c.577A>C

Your query was ambiguous. Multiple possible variants found:

• chr10-17695090-A-C
• chr10-17695090-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003473.4(STAM):​c.577A>C​(p.Thr193Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T193A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: STAM NM_003473.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.485

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.032135576).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAM	NM_003473.4	c.577A>C	p.Thr193Pro	missense_variant	Exon 7 of 14	ENST00000377524.8	NP_003464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAM	ENST00000377524.8	c.577A>C	p.Thr193Pro	missense_variant	Exon 7 of 14	1	NM_003473.4	ENSP00000366746.3
STAM	ENST00000377500.1	c.244A>C	p.Thr82Pro	missense_variant	Exon 4 of 6	5		ENSP00000366721.1
STAM	ENST00000494250.1	n.165A>C		non_coding_transcript_exon_variant	Exon 1 of 3	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	17
DANN	Benign	0.94
DEOGEN2	Benign	0.070	T;T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.44	T;T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.032	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.20	N;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.47	N;.
REVEL	Benign	0.044
Sift	Benign	0.23	T;.
Sift4G	Benign	0.23	T;T
Polyphen		0.0	B;.
Vest4		0.14
MutPred		0.26		Gain of phosphorylation at T192 (P = 0.0598);.;
MVP		0.25
MPC		0.12
ClinPred		0.090	T
GERP RS		-0.96
Varity_R		0.10
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

Other links and lift over

dbSNP: rs781788116; hg19: chr10-17737089;