11-120211337-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_178507.4(OAF):​c.58C>T​(p.Leu20Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000109 in 1,408,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

OAF
NM_178507.4 missense

Scores

1
1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.483
Variant links:
Genes affected
OAF (HGNC:28752): (out at first homolog)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.086643964).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OAFNM_178507.4 linkc.58C>T p.Leu20Phe missense_variant Exon 1 of 4 ENST00000328965.9 NP_848602.1 Q86UD1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OAFENST00000328965.9 linkc.58C>T p.Leu20Phe missense_variant Exon 1 of 4 1 NM_178507.4 ENSP00000332613.3 Q86UD1
OAFENST00000531220.1 linkc.-207C>T 5_prime_UTR_variant Exon 1 of 4 3 ENSP00000431865.1 E9PJ29

Frequencies

GnomAD3 genomes
AF:
0.000513
AC:
78
AN:
151968
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00179
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.000478
GnomAD4 exome
AF:
0.0000597
AC:
75
AN:
1256900
Hom.:
0
Cov.:
23
AF XY:
0.0000518
AC XY:
32
AN XY:
617186
show subpopulations
Gnomad4 AFR exome
AF:
0.00198
Gnomad4 AMR exome
AF:
0.0000570
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:
0.0000168
Gnomad4 OTH exome
AF:
0.000135
GnomAD4 genome
AF:
0.000513
AC:
78
AN:
151968
Hom.:
0
Cov.:
31
AF XY:
0.000323
AC XY:
24
AN XY:
74220
show subpopulations
Gnomad4 AFR
AF:
0.00179
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.000569
Hom.:
0
Bravo
AF:
0.000646

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 20, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.58C>T (p.L20F) alteration is located in exon 1 (coding exon 1) of the OAF gene. This alteration results from a C to T substitution at nucleotide position 58, causing the leucine (L) at amino acid position 20 to be replaced by a phenylalanine (F). 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
0.11
BayesDel_addAF
Benign
-0.55
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
11
DANN
Benign
0.89
DEOGEN2
Benign
0.0080
T
Eigen
Benign
-0.67
Eigen_PC
Benign
-0.75
FATHMM_MKL
Benign
0.61
D
LIST_S2
Benign
0.28
T
M_CAP
Uncertain
0.20
D
MetaRNN
Benign
0.087
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.1
L
PrimateAI
Pathogenic
0.87
D
PROVEAN
Benign
-0.21
N
REVEL
Benign
0.069
Sift
Benign
0.13
T
Sift4G
Benign
0.20
T
Polyphen
0.81
P
Vest4
0.24
MutPred
0.24
Loss of disorder (P = 0.0377);
MVP
0.20
MPC
0.56
ClinPred
0.25
T
GERP RS
-0.94
Varity_R
0.038
gMVP
0.27

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: rs950503738; hg19: chr11-120082045; API