1-200048501-C-T

Variant names:

• chr1-200048501-C-T
• rs778933557
• NM_205860.3:c.793C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.79

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]

ACMG classification

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
NR5A2	NM_205860.3	c.793C>T	p.Pro265Ser	missense_variant	Exon 5 of 8	ENST00000367362.8	NP_995582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR5A2	ENST00000367362.8	c.793C>T	p.Pro265Ser	missense_variant	Exon 5 of 8	1	NM_205860.3	ENSP00000356331.3
NR5A2	ENST00000236914.7	c.655C>T	p.Pro219Ser	missense_variant	Exon 4 of 7	1		ENSP00000236914.3
NR5A2	ENST00000367357.3	c.553C>T	p.Pro185Ser	missense_variant	Exon 3 of 4	1		ENSP00000356326.3
NR5A2	ENST00000544748.5	c.577C>T	p.Pro193Ser	missense_variant	Exon 4 of 7	2		ENSP00000439116.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152206 Hom.: 0 Cov.: 32

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

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

Other links and lift over

dbSNP: rs778933557; hg19: chr1-200017629;