NM_205860.3:c.565A>C

Variant names:

• chr1-200048273-A-C
• rs1662468369
• NM_205860.3:c.565A>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_205860.3(NR5A2):​c.565A>C​(p.Asn189His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,892 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.26
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_205860.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR5A2	NM_205860.3	MANE Select	c.565A>C	p.Asn189His	missense	Exon 5 of 8	NP_995582.1	O00482-1
	NR5A2	NM_003822.5		c.427A>C	p.Asn143His	missense	Exon 4 of 7	NP_003813.1	F1D8R9
	NR5A2	NM_001276464.2		c.349A>C	p.Asn117His	missense	Exon 4 of 7	NP_001263393.1	O00482-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR5A2	ENST00000367362.8	TSL:1 MANE Select	c.565A>C	p.Asn189His	missense	Exon 5 of 8	ENSP00000356331.3	O00482-1
	NR5A2	ENST00000236914.7	TSL:1	c.427A>C	p.Asn143His	missense	Exon 4 of 7	ENSP00000236914.3	O00482-2
	NR5A2	ENST00000367357.3	TSL:1	c.325A>C	p.Asn109His	missense	Exon 3 of 4	ENSP00000356326.3	H0Y328

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461892 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112010

Other (OTH) AF: 0.0000331 AC: 2 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.52	D
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Benign	0.63	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Uncertain	0.46	D
MutationAssessor	Benign	1.8	L
PhyloP100		9.3
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.44
Sift	Benign	0.074	T
Sift4G	Uncertain	0.054	T
Polyphen		0.12	B
Vest4		0.75
MutPred		0.33		Gain of catalytic residue at R187 (P = 0.0634)
MVP		0.86
MPC		0.51
ClinPred		0.91	D
GERP RS		5.8
Varity_R		0.50
gMVP		0.66
Mutation Taster		=28/72	disease causing

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

Other links and lift over

dbSNP: rs1662468369; hg19: chr1-200017401;