16-83965295-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_182981.3(OSGIN1):​c.722A>T​(p.Asn241Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000345 in 1,448,000 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: not found (cov: 33)
Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

OSGIN1
NM_182981.3 missense

Scores

5
12
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.01
Variant links:
Genes affected
OSGIN1 (HGNC:30093): (oxidative stress induced growth inhibitor 1) This gene encodes an oxidative stress response protein that regulates cell death. Expression of the gene is regulated by p53 and is induced by DNA damage. The protein regulates apoptosis by inducing cytochrome c release from mitochondria. It also appears to be a key regulator of both inflammatory and anti-inflammatory molecules. The loss of this protein correlates with uncontrolled cell growth and tumor formation. Naturally occurring read-through transcription exists between this gene and the neighboring upstream malonyl-CoA decarboxylase (MLYCD) gene, but the read-through transcripts are unlikely to produce a protein product. [provided by RefSeq, Aug 2011]
NECAB2 (HGNC:23746): (N-terminal EF-hand calcium binding protein 2) The protein encoded by this gene is a neuronal calcium-binding protein that binds to and modulates the function of at least two receptors, adenosine A(2A) receptor and metabotropic glutamate receptor type 5. [provided by RefSeq, Jul 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.901

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OSGIN1NM_182981.3 linkc.722A>T p.Asn241Ile missense_variant Exon 6 of 6 ENST00000393306.6 NP_892026.1 Q9UJX0
NECAB2XM_047434240.1 linkc.-23+59A>T intron_variant Intron 1 of 11 XP_047290196.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OSGIN1ENST00000393306.6 linkc.722A>T p.Asn241Ile missense_variant Exon 6 of 6 1 NM_182981.3 ENSP00000376983.1 Q9UJX0
OSGIN1ENST00000361711.7 linkc.722A>T p.Asn241Ile missense_variant Exon 6 of 6 2 ENSP00000355374.3 Q9UJX0
OSGIN1ENST00000343939.6 linkn.1354A>T non_coding_transcript_exon_variant Exon 7 of 7 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000345
AC:
5
AN:
1448000
Hom.:
0
Cov.:
34
AF XY:
0.00000417
AC XY:
3
AN XY:
718682
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:
0.0000470
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.64
BayesDel_addAF
Pathogenic
0.24
D
BayesDel_noAF
Uncertain
0.10
CADD
Uncertain
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.17
.;T;.
Eigen
Uncertain
0.58
Eigen_PC
Uncertain
0.55
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Uncertain
0.96
.;D;D
M_CAP
Uncertain
0.27
D
MetaRNN
Pathogenic
0.90
D;D;D
MetaSVM
Uncertain
0.077
D
MutationAssessor
Uncertain
2.9
.;M;.
PrimateAI
Uncertain
0.61
T
PROVEAN
Pathogenic
-7.3
D;D;D
REVEL
Pathogenic
0.75
Sift
Uncertain
0.0020
D;D;D
Sift4G
Uncertain
0.0080
D;D;D
Polyphen
1.0
.;D;.
Vest4
0.86
MutPred
0.69
.;Gain of sheet (P = 0.0477);.;
MVP
0.92
MPC
0.53
ClinPred
0.99
D
GERP RS
4.8
Varity_R
0.82
gMVP
0.51

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.

Other links and lift over

dbSNP: rs371530657; hg19: chr16-83998900; API