2-19353360-G-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_145260.3(OSR1):​c.446C>A​(p.Ala149Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000397 in 1,614,088 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000030 ( 2 hom. )

Consequence

OSR1
NM_145260.3 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.50

Publications

0 publications found
Variant links:
Genes affected
OSR1 (HGNC:8111): (odd-skipped related transcription factor 1) Enables sequence-specific double-stranded DNA binding activity. Involved in negative regulation of ion transmembrane transporter activity; positive regulation of gastrulation; and pronephros development. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.039557755).
BS2
High AC in GnomAd4 at 20 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OSR1NM_145260.3 linkc.446C>A p.Ala149Asp missense_variant Exon 2 of 3 ENST00000272223.3 NP_660303.1 Q8TAX0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OSR1ENST00000272223.3 linkc.446C>A p.Ala149Asp missense_variant Exon 2 of 3 1 NM_145260.3 ENSP00000272223.2 Q8TAX0
OSR1ENST00000487581.1 linkn.3553C>A non_coding_transcript_exon_variant Exon 1 of 2 1

Frequencies

GnomAD3 genomes
AF:
0.000131
AC:
20
AN:
152246
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000458
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000636
AC:
16
AN:
251380
AF XY:
0.0000662
show subpopulations
Gnomad AFR exome
AF:
0.000492
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000381
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000301
AC:
44
AN:
1461842
Hom.:
2
Cov.:
31
AF XY:
0.0000303
AC XY:
22
AN XY:
727226
show subpopulations
African (AFR)
AF:
0.000209
AC:
7
AN:
33480
American (AMR)
AF:
0.0000224
AC:
1
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.000252
AC:
10
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53404
Middle Eastern (MID)
AF:
0.000173
AC:
1
AN:
5768
European-Non Finnish (NFE)
AF:
0.00000360
AC:
4
AN:
1111986
Other (OTH)
AF:
0.000348
AC:
21
AN:
60386
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.491
Heterozygous variant carriers
0
3
6
10
13
16
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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:
0.000131
AC:
20
AN:
152246
Hom.:
0
Cov.:
33
AF XY:
0.000202
AC XY:
15
AN XY:
74388
show subpopulations
African (AFR)
AF:
0.000458
AC:
19
AN:
41472
American (AMR)
AF:
0.00
AC:
0
AN:
15294
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3468
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5192
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4834
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10624
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
68040
Other (OTH)
AF:
0.00
AC:
0
AN:
2094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.483
Heterozygous variant carriers
0
1
3
4
6
7
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.000115
Hom.:
0
Bravo
AF:
0.000144
ESP6500AA
AF:
0.000681
AC:
3
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000576
AC:
7
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 04, 2023
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.446C>A (p.A149D) alteration is located in exon 2 (coding exon 1) of the OSR1 gene. This alteration results from a C to A substitution at nucleotide position 446, causing the alanine (A) at amino acid position 149 to be replaced by an aspartic acid (D). 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
Benign
0.27
BayesDel_addAF
Benign
-0.44
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.13
T
Eigen
Benign
-0.35
Eigen_PC
Benign
-0.20
FATHMM_MKL
Uncertain
0.76
D
LIST_S2
Uncertain
0.87
D
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.040
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N
PhyloP100
1.5
PrimateAI
Uncertain
0.55
T
PROVEAN
Benign
-0.93
N
REVEL
Benign
0.13
Sift
Benign
0.28
T
Sift4G
Benign
0.19
T
Polyphen
0.060
B
Vest4
0.15
MVP
0.40
ClinPred
0.023
T
GERP RS
5.1
Varity_R
0.24
gMVP
0.68
Mutation Taster
=79/21
polymorphism

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

Other links and lift over

dbSNP: rs149742000; hg19: chr2-19553121; API