3-31533054-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_178862.3(STT3B):c.56C>T(p.Pro19Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,431,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: STT3B NM_178862.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.11

Genes affected

STT3B (HGNC:30611): (STT3 oligosaccharyltransferase complex catalytic subunit B) The protein encoded by this gene is a catalytic subunit of a protein complex that transfers oligosaccharides onto asparagine residues. Defects in this gene are a cause of congenital disorder of glycosylation Ix (CDG1X). [provided by RefSeq, Jun 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, STT3B
• BP4: Computational evidence support a benign effect (MetaRNN=0.15948588).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STT3B	NM_178862.3	c.56C>T	p.Pro19Leu	missense_variant	1/16	ENST00000295770.4
STT3B	XM_011533465.2	c.56C>T	p.Pro19Leu	missense_variant	1/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STT3B	ENST00000295770.4	c.56C>T	p.Pro19Leu	missense_variant	1/16	1	NM_178862.3	P1
STT3B	ENST00000453168.5	n.417C>T		non_coding_transcript_exon_variant	1/10	1
STT3B	ENST00000423527.5	n.83C>T		non_coding_transcript_exon_variant	1/10	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.99e-7 AC: 1 AN: 1431550 Hom.: 0 Cov.: 32 AF XY: 0.00000140 AC XY: 1 AN XY: 712110

Gnomad4 AFR exome AF: 0.0000337

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 30, 2021

The c.56C>T (p.P19L) alteration is located in exon 1 (coding exon 1) of the STT3B gene. This alteration results from a C to T substitution at nucleotide position 56, causing the proline (P) at amino acid position 19 to be replaced by a leucine (L). 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	0.13
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
Cadd	Uncertain	25
Dann	Uncertain	0.99
DEOGEN2	Benign	0.093	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.64	T
M_CAP	Pathogenic	0.74	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
MutationTaster	Benign	0.92	D
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.90	N
REVEL	Benign	0.033
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.046	D
Polyphen		0.0	B
Vest4		0.13
MutPred		0.21		Gain of helix (P = 0.0078);
MVP		0.10
MPC		0.86
ClinPred		0.58	D
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.14
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.

Other links and lift over

hg19: chr3-31574546;