Genetic Variant ENST00000527606.5:c.-36+834T>A (chr11-125592721-T-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000527606.5(STT3A):c.-36+834T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00579 in 291,758 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0097 ( 26 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 3 hom. )

Consequence

STT3A
ENST00000527606.5 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.492

Publications

0 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 11-125592721-T-A is Benign according to our data. Variant chr11-125592721-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1318192.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0097 (1477/152264) while in subpopulation AFR AF = 0.0319 (1326/41552). AF 95% confidence interval is 0.0305. There are 26 homozygotes in GnomAd4. There are 695 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 26 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000527606.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
STT3A	NM_152713.5	MANE Select	c.-233T>A	upstream_gene	N/A	NP_689926.1	P46977-1
STT3A	NM_001278503.2		c.-321T>A	upstream_gene	N/A	NP_001265432.1	P46977-1
STT3A	NM_001278504.2		c.-386T>A	upstream_gene	N/A	NP_001265433.1	P46977-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
STT3A	ENST00000527606.5	TSL:4	c.-36+834T>A	intron	N/A	ENSP00000436558.1	E9PI32
STT3A	ENST00000392708.9	TSL:1 MANE Select	c.-233T>A	upstream_gene	N/A	ENSP00000376472.3	P46977-1
STT3A	ENST00000529196.5	TSL:1	c.-321T>A	upstream_gene	N/A	ENSP00000436962.1	P46977-1

Frequencies

GnomAD3 genomes

AF:

0.00967

AC:

1471

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0319

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00635

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.00765

GnomAD4 exome

AF:

0.00152

AC:

212

AN:

139494

Hom.:

Cov.:

AF XY:

0.00159

AC XY:

125

AN XY:

78420

show subpopulations

African (AFR)

AF:

0.0296

AC:

101

AN:

3408

American (AMR)

AF:

0.00277

AC:

AN:

6858

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2824

East Asian (EAS)

AF:

0.00

AC:

AN:

4846

South Asian (SAS)

AF:

0.00189

AC:

AN:

32818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6418

Middle Eastern (MID)

AF:

0.00234

AC:

AN:

428

European-Non Finnish (NFE)

AF:

0.000252

AC:

AN:

75504

Other (OTH)

AF:

0.00156

AC:

AN:

6390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

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:

0.00970

AC:

1477

AN:

152264

Hom.:

Cov.:

AF XY:

0.00933

AC XY:

695

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0319

AC:

1326

AN:

41552

American (AMR)

AF:

0.00634

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00352

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000294

AC:

AN:

68012

Other (OTH)

AF:

0.00757

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

151

226

302

377

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00

Hom.:

Bravo

AF:

0.0112

Asia WGS

AF:

0.00260

AC:

AN:

3476

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

6.1

(source)

DANN

Benign

0.28

PhyloP100

0.49

PromoterAI

0.065

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over