4-108650764-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_021227.4(OSTC):​c.109G>A​(p.Val37Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,614,250 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000098 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

OSTC
NM_021227.4 missense

Scores

7
8
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.24
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.746

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OSTCNM_021227.4 linkuse as main transcriptc.109G>A p.Val37Met missense_variant 1/4 ENST00000361564.9 NP_067050.1 Q9NRP0-1A0A024RDJ1
OSTCNM_001267818.2 linkuse as main transcriptc.109G>A p.Val37Met missense_variant 1/5 NP_001254747.1 Q9NRP0-2
OSTCNM_001267817.2 linkuse as main transcriptc.109G>A p.Val37Met missense_variant 1/3 NP_001254746.1 Q9NRP0A0A087WUD3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OSTCENST00000361564.9 linkuse as main transcriptc.109G>A p.Val37Met missense_variant 1/41 NM_021227.4 ENSP00000354676.4 Q9NRP0-1

Frequencies

GnomAD3 genomes
AF:
0.0000985
AC:
15
AN:
152246
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000362
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
251128
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135770
show subpopulations
Gnomad AFR exome
AF:
0.000369
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461886
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000984
AC:
15
AN:
152364
Hom.:
0
Cov.:
33
AF XY:
0.000134
AC XY:
10
AN XY:
74508
show subpopulations
Gnomad4 AFR
AF:
0.000361
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000793
ESP6500AA
AF:
0.000454
AC:
2
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000412
AC:
5

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 submitterclinical testingAmbry GeneticsAug 05, 2024The c.109G>A (p.V37M) alteration is located in exon 1 (coding exon 1) of the OSTC gene. This alteration results from a G to A substitution at nucleotide position 109, causing the valine (V) at amino acid position 37 to be replaced by a methionine (M). 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
0.73
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Pathogenic
0.33
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.13
T;T;.
Eigen
Uncertain
0.36
Eigen_PC
Uncertain
0.47
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.87
D;D;D
M_CAP
Pathogenic
0.33
D
MetaRNN
Pathogenic
0.75
D;D;D
MetaSVM
Uncertain
-0.15
T
MutationAssessor
Uncertain
2.5
M;.;M
PrimateAI
Pathogenic
0.87
D
PROVEAN
Benign
-2.2
N;.;N
REVEL
Pathogenic
0.67
Sift
Benign
0.042
D;.;D
Sift4G
Uncertain
0.033
D;D;D
Polyphen
0.099
B;.;.
Vest4
0.95
MVP
0.93
MPC
0.63
ClinPred
0.56
D
GERP RS
5.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.71
gMVP
0.91

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs138808989; hg19: chr4-109571920; API