Genetic Variant STT3A:c.-109A>G (chr11-125591814-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000527606.5(STT3A):c.-109A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.833 in 152,326 control chromosomes in the GnomAD database, including 53,295 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.83 ( 53210 hom., cov: 31)

Exomes 𝑓: 0.92 ( 85 hom. )

Consequence

STT3A
ENST00000527606.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.70

Publications

38 publications found

Variant links:

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]

STT3A links:

FEZ1 (HGNC:3659): (fasciculation and elongation protein zeta 1) This gene is an ortholog of the C. elegans unc-76 gene, which is necessary for normal axonal bundling and elongation within axon bundles. Expression of this gene in C. elegans unc-76 mutants can restore to the mutants partial locomotion and axonal fasciculation, suggesting that it also functions in axonal outgrowth. The N-terminal half of the gene product is highly acidic. Alternatively spliced transcript variants encoding different isoforms of this protein have been described. [provided by RefSeq, Jul 2008]

FEZ1 links:

STT3A-AS1 (HGNC:44585): (STT3A antisense RNA 1)

STT3A-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STT3A	XM_047426897.1 link	c.-325A>G		5_prime_UTR_variant	Exon 1 of 19		XP_047282853.1
STT3A-AS1	NR_132372.1 link	n.151+604T>C		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
STT3A	ENST00000527606.5 link	c.-109A>G	5_prime_UTR_variant	Exon 1 of 5	4	ENSP00000436558.1
FEZ1	ENST00000648911.1 link	c.-259+604T>C	intron_variant	Intron 1 of 11		ENSP00000497070.1
FEZ1	ENST00000530526.1 link	n.151+604T>C	intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.833

AC:

126614

AN:

152006

Hom.:

53175

Cov.:

show subpopulations

Gnomad AFR

AF:

0.714

Gnomad AMI

AF:

0.885

Gnomad AMR

AF:

0.858

Gnomad ASJ

AF:

0.879

Gnomad EAS

AF:

0.884

Gnomad SAS

AF:

0.941

Gnomad FIN

AF:

0.815

Gnomad MID

AF:

0.889

Gnomad NFE

AF:

0.887

Gnomad OTH

AF:

0.854

GnomAD4 exome

AF:

0.916

AC:

185

AN:

202

Hom.:

Cov.:

AF XY:

0.934

AC XY:

114

AN XY:

122

show subpopulations

African (AFR)

AF:

0.667

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

0.833

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.881

AC:

104

AN:

118

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.833

AC:

126697

AN:

152124

Hom.:

53210

Cov.:

AF XY:

0.832

AC XY:

61847

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.714

AC:

29608

AN:

41492

American (AMR)

AF:

0.857

AC:

13112

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.879

AC:

3049

AN:

3470

East Asian (EAS)

AF:

0.884

AC:

4564

AN:

5164

South Asian (SAS)

AF:

0.942

AC:

4548

AN:

4828

European-Finnish (FIN)

AF:

0.815

AC:

8608

AN:

10560

Middle Eastern (MID)

AF:

0.891

AC:

262

AN:

294

European-Non Finnish (NFE)

AF:

0.887

AC:

60336

AN:

68004

Other (OTH)

AF:

0.855

AC:

1805

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1071

2142

3213

4284

5355

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

888

1776

2664

3552

4440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.872

Hom.:

229675

Bravo

AF:

0.827

Asia WGS

AF:

0.887

AC:

3084

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.3

(source)

DANN

Benign

0.47

PhyloP100

-1.7

PromoterAI

-0.0072

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over