3-31533036-C-A

Variant names:

• chr3-31533036-C-A
• rs1696976315
• NM_178862.3:c.38C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_178862.3(STT3B):​c.38C>A​(p.Ser13*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000697 in 1,435,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: STT3B NM_178862.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.59
• Publications: 0 publications found

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]

STT3B Gene-Disease associations (from GenCC):

• STT3B-congenital disorder of glycosylation

  Inheritance: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: G2P, PanelApp Australia, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ENSG00000288926 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178862.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STT3B	NM_178862.3	MANE Select	c.38C>A	p.Ser13*	stop_gained	Exon 1 of 16	NP_849193.1	Q8TCJ2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STT3B	ENST00000295770.4	TSL:1 MANE Select	c.38C>A	p.Ser13*	stop_gained	Exon 1 of 16	ENSP00000295770.2	Q8TCJ2
	STT3B	ENST00000453168.5	TSL:1	n.399C>A		non_coding_transcript_exon	Exon 1 of 10
	STT3B	ENST00000935233.1		c.38C>A	p.Ser13*	stop_gained	Exon 1 of 16	ENSP00000605292.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.97e-7 AC: 1 AN: 1435546 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 714158

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 29914

American (AMR) AF: 0.00 AC: 0 AN: 43058

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25156

East Asian (EAS) AF: 0.00 AC: 0 AN: 35196

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85118

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1100536

Other (OTH) AF: 0.00 AC: 0 AN: 59280

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.53	D
BayesDel_noAF	Pathogenic	0.52
CADD	Pathogenic	43
DANN	Uncertain	0.99
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.86	D
PhyloP100		3.6
Vest4		0.11
GERP RS		3.7
PromoterAI		-0.068	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=7/193	disease causing (fs/PTC)

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

Other links and lift over

dbSNP: rs1696976315; hg19: chr3-31574528;