Genetic Variant ENST00000526364.1:n.529C>T (chr11-125625127-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000526364.1(STT3A):n.529C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 221,698 control chromosomes in the GnomAD database, including 2,595 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 0.13 ( 1767 hom., cov: 32)

Exomes 𝑓: 0.15 ( 828 hom. )

Consequence

STT3A
ENST00000526364.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.672

Publications

10 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:

ENSG00000288907 (HGNC:):

ENSG00000288907 links:

CHEK1 (HGNC:1925): (checkpoint kinase 1) The protein encoded by this gene belongs to the Ser/Thr protein kinase family. It is required for checkpoint mediated cell cycle arrest in response to DNA damage or the presence of unreplicated DNA. This protein acts to integrate signals from ATM and ATR, two cell cycle proteins involved in DNA damage responses, that also associate with chromatin in meiotic prophase I. Phosphorylation of CDC25A protein phosphatase by this protein is required for cells to delay cell cycle progression in response to double-strand DNA breaks. Several alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Oct 2011]

CHEK1 Gene-Disease associations (from GenCC):

familial ovarian cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
hereditary breast carcinoma
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

CHEK1 links:

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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=-0.81).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHEK1	NM_001114122.3 link	c.-906C>T		upstream_gene_variant		ENST00000438015.7	NP_001107594.1	O14757-1B4DT73

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
STT3A	ENST00000526364.1 link	n.529C>T	non_coding_transcript_exon_variant	Exon 4 of 4	3
ENSG00000288907	ENST00000686400.3 link	n.792G>A	non_coding_transcript_exon_variant	Exon 1 of 1
CHEK1	ENST00000438015.7 link	c.-906C>T	upstream_gene_variant		5	NM_001114122.3	ENSP00000388648.1	O14757-1

Frequencies

GnomAD3 genomes

AF:

0.129

AC:

19665

AN:

152096

Hom.:

1763

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0359

Gnomad AMI

AF:

0.225

Gnomad AMR

AF:

0.291

Gnomad ASJ

AF:

0.143

Gnomad EAS

AF:

0.178

Gnomad SAS

AF:

0.131

Gnomad FIN

AF:

0.116

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.146

Gnomad OTH

AF:

0.145

GnomAD4 exome

AF:

0.147

AC:

10230

AN:

69484

Hom.:

828

Cov.:

AF XY:

0.149

AC XY:

4778

AN XY:

32074

show subpopulations

African (AFR)

AF:

0.0320

AC:

105

AN:

3286

American (AMR)

AF:

0.320

AC:

652

AN:

2040

Ashkenazi Jewish (ASJ)

AF:

0.154

AC:

682

AN:

4416

East Asian (EAS)

AF:

0.205

AC:

2047

AN:

9996

South Asian (SAS)

AF:

0.122

AC:

AN:

622

European-Finnish (FIN)

AF:

0.0926

AC:

AN:

Middle Eastern (MID)

AF:

0.0860

AC:

AN:

430

European-Non Finnish (NFE)

AF:

0.136

AC:

5823

AN:

42880

Other (OTH)

AF:

0.139

AC:

803

AN:

5760

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

439

877

1316

1754

2193

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

160

200

<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:

0.129

AC:

19662

AN:

152214

Hom.:

1767

Cov.:

AF XY:

0.131

AC XY:

9740

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.0358

AC:

1486

AN:

41558

American (AMR)

AF:

0.291

AC:

4454

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.143

AC:

496

AN:

3470

East Asian (EAS)

AF:

0.178

AC:

921

AN:

5172

South Asian (SAS)

AF:

0.130

AC:

625

AN:

4814

European-Finnish (FIN)

AF:

0.116

AC:

1222

AN:

10578

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.146

AC:

9916

AN:

68012

Other (OTH)

AF:

0.144

AC:

305

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

868

1737

2605

3474

4342

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

208

416

624

832

1040

<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:

0.146

Hom.:

4020

Bravo

AF:

0.139

Asia WGS

AF:

0.171

AC:

592

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.0

(source)

DANN

Benign

0.69

PhyloP100

-0.67

PromoterAI

-0.12

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(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