1-200039721-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_205860.3(NR5A2):​c.128C>T​(p.Pro43Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,112 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

NR5A2
NM_205860.3 missense

Scores

6
8
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.19
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NR5A2NM_205860.3 linkc.128C>T p.Pro43Leu missense_variant Exon 2 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.128C>T p.Pro43Leu missense_variant Exon 2 of 8 1 NM_205860.3 ENSP00000356331.3 O00482-1
NR5A2ENST00000447034.1 linkc.164C>T p.Pro55Leu missense_variant Exon 3 of 3 1 ENSP00000414888.1 H0Y7S7
NR5A2ENST00000236914.7 linkc.65-4053C>T intron_variant Intron 1 of 6 1 ENSP00000236914.3 O00482-2
NR5A2ENST00000474307.1 linkn.*419-4053C>T intron_variant Intron 2 of 2 1 ENSP00000436776.1 E9PQH2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000401
AC:
1
AN:
249500
Hom.:
0
AF XY:
0.00000740
AC XY:
1
AN XY:
135122
show subpopulations
Gnomad AFR exome
AF:
0.00
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:
0.00000886
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1460112
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
726456
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 02, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.128C>T (p.P43L) alteration is located in exon 2 (coding exon 2) of the NR5A2 gene. This alteration results from a C to T substitution at nucleotide position 128, causing the proline (P) at amino acid position 43 to be replaced by a leucine (L). 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
0.95
BayesDel_addAF
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.17
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.42
T
Eigen
Benign
-0.046
Eigen_PC
Benign
0.15
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Uncertain
0.95
D
M_CAP
Pathogenic
0.96
D
MetaRNN
Uncertain
0.66
D
MetaSVM
Uncertain
0.026
D
MutationAssessor
Benign
0.97
L
PrimateAI
Pathogenic
0.88
D
PROVEAN
Benign
-1.6
N
REVEL
Uncertain
0.59
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.0090
D
Polyphen
0.079
B
Vest4
0.59
MutPred
0.58
Loss of disorder (P = 0.0255);
MVP
0.78
MPC
0.44
ClinPred
0.56
D
GERP RS
5.0
Varity_R
0.52
gMVP
0.71

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: rs769544083; hg19: chr1-200008849; API