3-31532901-TTCCTCCTCC-TTCCTCCTCCTCCTCCTCCTCC

Variant names:

• chr3-31532901-T-TTCCTCCTCCTCC
• rs529181821
• ENST00000453168.5:n.274_285dupTCCTCCTCCTCC

Variant summary

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

The ENST00000935233.1(STT3B):​c.-88_-77dupTCCTCCTCCTCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000161 in 1,244,936 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: STT3B ENST00000935233.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.833
• Publications: 1 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 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000935233.1. 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.-98_-97insTCCTCCTCCTCC		upstream_gene	N/A	NP_849193.1	Q8TCJ2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STT3B	ENST00000453168.5	TSL:1	n.274_285dupTCCTCCTCCTCC		non_coding_transcript_exon	Exon 1 of 10
	STT3B	ENST00000935233.1		c.-88_-77dupTCCTCCTCCTCC		5_prime_UTR	Exon 1 of 16	ENSP00000605292.1
	STT3B	ENST00000868023.1		c.-88_-77dupTCCTCCTCCTCC		5_prime_UTR	Exon 1 of 15	ENSP00000538082.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000161 AC: 2 AN: 1244936 Hom.: 0 Cov.: 31 AF XY: 0.00000328 AC XY: 2 AN XY: 609060

⚠️ 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: 24724

American (AMR) AF: 0.00 AC: 0 AN: 13996

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17672

East Asian (EAS) AF: 0.00 AC: 0 AN: 27734

South Asian (SAS) AF: 0.00 AC: 0 AN: 58834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4510

European-Non Finnish (NFE) AF: 0.00000199 AC: 2 AN: 1005592

Other (OTH) AF: 0.00 AC: 0 AN: 50300

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000203476), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.83

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs529181821; hg19: chr3-31574393;