Variant 4-108655631-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021227.4(OSTC):c.207G>C(p.Gln69His) variant causes a missense change. The variant allele was found at a frequency of 0.0000603 in 1,608,298 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

OSTC
NM_021227.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.48

Variant links:

Genes affected

OSTC (HGNC:24448): (oligosaccharyltransferase complex non-catalytic subunit) Predicted to contribute to dolichyl-diphosphooligosaccharide-protein glycotransferase activity. Predicted to be involved in protein N-linked glycosylation via asparagine. Part of oligosaccharyltransferase complex. [provided by Alliance of Genome Resources, Apr 2022]

OSTC links:

OSTC (HGNC:):

OSTC links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSTC	NM_021227.4 linkuse as main transcript	c.207G>C	p.Gln69His	missense_variant	2/4	ENST00000361564.9	NP_067050.1	Q9NRP0-1A0A024RDJ1
OSTC	NM_001267818.2 linkuse as main transcript	c.207G>C	p.Gln69His	missense_variant	2/5		NP_001254747.1	Q9NRP0-2
OSTC	NM_001267817.2 linkuse as main transcript	c.207G>C	p.Gln69His	missense_variant	2/3		NP_001254746.1	Q9NRP0A0A087WUD3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OSTC	ENST00000361564.9 linkuse as main transcript	c.207G>C	p.Gln69His	missense_variant	2/4	1	NM_021227.4	ENSP00000354676.4	Q9NRP0-1
OSTC	ENST00000512478.2 linkuse as main transcript	c.207G>C	p.Gln69His	missense_variant	2/5	5		ENSP00000426167.2	Q9NRP0-2
OSTC	ENST00000613215.4 linkuse as main transcript	c.207G>C	p.Gln69His	missense_variant	2/3	2		ENSP00000478564.1	A0A087WUD3
OSTC	ENST00000510556.1 linkuse as main transcript	n.169-1819G>C		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000479

AC:

AN:

250338

Hom.:

AF XY:

0.0000370

AC XY:

AN XY:

135262

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000639

AC:

AN:

1456098

Hom.:

Cov.:

AF XY:

0.0000497

AC XY:

AN XY:

724662

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000840

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000675

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 10, 2024

The c.207G>C (p.Q69H) alteration is located in exon 2 (coding exon 2) of the OSTC gene. This alteration results from a G to C substitution at nucleotide position 207, causing the glutamine (Q) at amino acid position 69 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Uncertain

0.029

BayesDel_noAF

Uncertain

0.020

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.046

T;T;.

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.81

T;D;T

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.64

D;D;D

MetaSVM

Uncertain

-0.21

MutationAssessor

Benign

1.8

L;.;L

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-2.1

N;.;N

REVEL

Uncertain

0.55

Sift

Benign

0.56

T;.;T

Sift4G

Benign

0.17

T;T;T

Polyphen

0.71

P;.;.

Vest4

0.69

MutPred

0.35

Loss of sheet (P = 0.1398);Loss of sheet (P = 0.1398);Loss of sheet (P = 0.1398);

MVP

0.65

MPC

1.1

ClinPred

0.56

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.34

gMVP

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over