11-125595980-T-C

Position:

• chr11-125595980-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP2 PP3

The NM_152713.5(STT3A):​c.65T>C​(p.Ile22Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: STT3A NM_152713.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.67

Genes affected

STT3A (HGNC:6172): (STT3 oligosaccharyltransferase complex catalytic subunit A) The protein encoded by this gene is a catalytic subunit of the N-oligosaccharyltransferase (OST) complex, which functions in the endoplasmic reticulum to transfer glycan chains to asparagine residues of target proteins. A separate complex containing a similar catalytic subunit with an overlapping function also exists. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), STT3A. . Gene score misZ 3.6202 (greater than the threshold 3.09). Trascript score misZ 4.4288 (greater than threshold 3.09). GenCC has associacion of gene with STT3A-congenital disorder of glycosylation, congenital disorder of glycosylation, type Iw, autosomal dominant.
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.839

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STT3A	NM_152713.5	c.65T>C	p.Ile22Thr	missense_variant	2/18	ENST00000392708.9	NP_689926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STT3A	ENST00000392708.9	c.65T>C	p.Ile22Thr	missense_variant	2/18	1	NM_152713.5	ENSP00000376472	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2021

The c.65T>C (p.I22T) alteration is located in exon 2 (coding exon 1) of the STT3A gene. This alteration results from a T to C substitution at nucleotide position 65, causing the isoleucine (I) at amino acid position 22 to be replaced by a threonine (T). 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	Pathogenic	0.79
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.34
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T;T;T;T;T;.
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D;.;.;D;D;D
M_CAP	Benign	0.017	T
MetaRNN	Pathogenic	0.84	D;D;D;D;D;D
MetaSVM	Benign	-0.45	T
MutationAssessor	Uncertain	2.5	.;M;M;M;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.93	D
PROVEAN	Uncertain	-4.2	D;D;D;.;D;D
REVEL	Uncertain	0.39
Sift	Benign	0.047	D;T;T;.;T;T
Sift4G	Benign	0.062	T;T;T;.;T;T
Polyphen		0.090	.;B;B;B;.;.
Vest4		0.88, 0.88
MutPred		0.73		Loss of stability (P = 0.0332);Loss of stability (P = 0.0332);Loss of stability (P = 0.0332);Loss of stability (P = 0.0332);Loss of stability (P = 0.0332);Loss of stability (P = 0.0332);
MVP		0.56
MPC		1.9
ClinPred		0.99	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.66
gMVP		0.96

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.

Other links and lift over

hg19: chr11-125465875;