rs34176522

Variant names:

• chr3-31624950-C-T
• rs34176522
• NM_178862.3:c.1764C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-31624950-C-T
• chr3-31624950-C-G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_178862.3(STT3B):​c.1764C>T​(p.Tyr588Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00162 in 1,612,714 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0070 (10 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (15 hom.)
• Consequence: STT3B NM_178862.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.49
• Publications: 2 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)

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 3-31624950-C-T is Benign according to our data. Variant chr3-31624950-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 385858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.49 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00705 (1072/152104) while in subpopulation AFR AF = 0.0239 (990/41482). AF 95% confidence interval is 0.0226. There are 10 homozygotes in GnomAd4. There are 500 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 10 AR,Unknown gene

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.1764C>T	p.Tyr588Tyr	synonymous	Exon 12 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.1764C>T	p.Tyr588Tyr	synonymous	Exon 12 of 16	ENSP00000295770.2	Q8TCJ2
	STT3B	ENST00000935233.1		c.1758C>T	p.Tyr586Tyr	synonymous	Exon 12 of 16	ENSP00000605292.1
	STT3B	ENST00000868023.1		c.1698C>T	p.Tyr566Tyr	synonymous	Exon 11 of 15	ENSP00000538082.1

Frequencies

GnomAD3 genomes AF: 0.00697 AC: 1059 AN: 151986 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.0236

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00321

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00236 AC: 590 AN: 250420 AF XY: 0.00194

Gnomad AFR exome AF: 0.0252

Gnomad AMR exome AF: 0.00166

Gnomad ASJ exome AF: 0.0000995

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000212

Gnomad OTH exome AF: 0.00148

GnomAD4 exome AF: 0.00106 AC: 1546 AN: 1460610 Hom.: 15 Cov.: 30 AF XY: 0.00104 AC XY: 759 AN XY: 726626

African (AFR) AF: 0.0270 AC: 902 AN: 33440

American (AMR) AF: 0.00181 AC: 81 AN: 44632

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26094

East Asian (EAS) AF: 0.00 AC: 0 AN: 39634

South Asian (SAS) AF: 0.00304 AC: 262 AN: 86122

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53330

Middle Eastern (MID) AF: 0.00712 AC: 41 AN: 5756

European-Non Finnish (NFE) AF: 0.000111 AC: 123 AN: 1111278

Other (OTH) AF: 0.00227 AC: 137 AN: 60324

GnomAD4 genome AF: 0.00705 AC: 1072 AN: 152104 Hom.: 10 Cov.: 32 AF XY: 0.00672 AC XY: 500 AN XY: 74356

African (AFR) AF: 0.0239 AC: 990 AN: 41482

American (AMR) AF: 0.00321 AC: 49 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000177 AC: 12 AN: 67988

Other (OTH) AF: 0.00473 AC: 10 AN: 2114

Alfa AF: 0.00690 Hom.: 4

Bravo AF: 0.00862

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	STT3B-congenital disorder of glycosylation (2)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	5.9
DANN	Benign	0.43
PhyloP100		1.5
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs34176522; hg19: chr3-31666442; COSMIC: COSV105889701; COSMIC: COSV105889701;