1-200048501-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_205860.3(NR5A2):​c.793C>T​(p.Pro265Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P265A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

NR5A2
NM_205860.3 missense

Scores

6
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.79
Variant links:
Genes affected
NR5A2 (HGNC:7984): (nuclear receptor subfamily 5 group A member 2) The protein encoded by this gene is a DNA-binding zinc finger transcription factor and is a member of the fushi tarazu factor-1 subfamily of orphan nuclear receptors. The encoded protein is involved in the expression of genes for hepatitis B virus and cholesterol biosynthesis, and may be an important regulator of embryonic development. [provided by RefSeq, Jun 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.29283798).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NR5A2NM_205860.3 linkc.793C>T p.Pro265Ser missense_variant Exon 5 of 8 ENST00000367362.8 NP_995582.1 O00482-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NR5A2ENST00000367362.8 linkc.793C>T p.Pro265Ser missense_variant Exon 5 of 8 1 NM_205860.3 ENSP00000356331.3 O00482-1
NR5A2ENST00000236914.7 linkc.655C>T p.Pro219Ser missense_variant Exon 4 of 7 1 ENSP00000236914.3 O00482-2
NR5A2ENST00000367357.3 linkc.553C>T p.Pro185Ser missense_variant Exon 3 of 4 1 ENSP00000356326.3 H0Y328
NR5A2ENST00000544748.5 linkc.577C>T p.Pro193Ser missense_variant Exon 4 of 7 2 ENSP00000439116.1 O00482-4

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152206
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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
GnomAD4 exome
Cov.:
34
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152206
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74364
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.077
BayesDel_addAF
Uncertain
0.13
D
BayesDel_noAF
Uncertain
-0.050
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.37
T;.;.
Eigen
Benign
-0.16
Eigen_PC
Benign
0.021
FATHMM_MKL
Benign
0.38
N
LIST_S2
Uncertain
0.88
D;D;D
M_CAP
Benign
0.076
D
MetaRNN
Benign
0.29
T;T;T
MetaSVM
Uncertain
-0.068
T
MutationAssessor
Benign
0.34
N;.;.
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-1.6
N;N;N
REVEL
Benign
0.26
Sift
Benign
0.17
T;T;T
Sift4G
Benign
0.24
T;T;T
Polyphen
0.015
B;.;.
Vest4
0.51
MutPred
0.17
Gain of phosphorylation at P265 (P = 0.0863);.;.;
MVP
0.55
MPC
0.44
ClinPred
0.85
D
GERP RS
4.2
Varity_R
0.22
gMVP
0.54

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: rs778933557; hg19: chr1-200017629; API