chr1-200174153-C-G

Variant names:

• chr1-200174153-C-G
• rs1060060
• NM_205860.3:c.1569C>G

Variant summary

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

The NM_205860.3(NR5A2):​c.1569C>G​(p.Asn523Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. N523S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 28)
• Consequence: NR5A2 NM_205860.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.63
• Publications: 22 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR5A2	NM_205860.3	c.1569C>G	p.Asn523Lys	missense_variant	Exon 8 of 8	ENST00000367362.8	NP_995582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR5A2	ENST00000367362.8	c.1569C>G	p.Asn523Lys	missense_variant	Exon 8 of 8	1	NM_205860.3	ENSP00000356331.3
NR5A2	ENST00000236914.7	c.1431C>G	p.Asn477Lys	missense_variant	Exon 7 of 7	1		ENSP00000236914.3
NR5A2	ENST00000544748.5	c.1353C>G	p.Asn451Lys	missense_variant	Exon 7 of 7	2		ENSP00000439116.1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 28

Alfa AF: 0.00 Hom.: 11069

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.020
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.45	T;.;.
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.31	N
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.58	D;D;D
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.85	L;.;.
PhyloP100		-2.6
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.16
Sift	Benign	0.28	T;T;T
Sift4G	Benign	0.39	T;T;T
Polyphen		0.97	D;.;.
Vest4		0.51
MutPred		0.61		Gain of ubiquitination at N523 (P = 0.0408);.;.;
MVP		0.43
MPC		0.67
ClinPred		0.46	T
GERP RS		-0.31
Varity_R		0.64
gMVP		0.54
Mutation Taster		=24/76	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: rs1060060; hg19: chr1-200143281;