chr1-200120881-T-C
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_205860.3(NR5A2):c.1304T>C(p.Val435Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,611,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000018 ( 0 hom. )
Consequence
NR5A2
NM_205860.3 missense
NM_205860.3 missense
Scores
6
6
7
Clinical Significance
Conservation
PhyloP100: 7.98
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.812
BS2
?
High AC in GnomAd at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NR5A2 | NM_205860.3 | c.1304T>C | p.Val435Ala | missense_variant | 7/8 | ENST00000367362.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NR5A2 | ENST00000367362.8 | c.1304T>C | p.Val435Ala | missense_variant | 7/8 | 1 | NM_205860.3 | A1 | |
NR5A2 | ENST00000236914.7 | c.1166T>C | p.Val389Ala | missense_variant | 6/7 | 1 | A1 | ||
NR5A2 | ENST00000544748.5 | c.1088T>C | p.Val363Ala | missense_variant | 6/7 | 2 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152214Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000161 AC: 4AN: 248850Hom.: 0 AF XY: 0.0000223 AC XY: 3AN XY: 134490
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GnomAD4 exome AF: 0.0000178 AC: 26AN: 1459698Hom.: 0 Cov.: 31 AF XY: 0.0000179 AC XY: 13AN XY: 726124
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GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152214Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74360
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 04, 2022 | The c.1304T>C (p.V435A) alteration is located in exon 7 (coding exon 7) of the NR5A2 gene. This alteration results from a T to C substitution at nucleotide position 1304, causing the valine (V) at amino acid position 435 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Benign
Dann
Uncertain
DEOGEN2
Uncertain
D;.;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Pathogenic
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
B;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at