chr1-200048604-C-T

Variant names:

• chr1-200048604-C-T
• NM_205860.3:c.896C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_205860.3(NR5A2):​c.896C>T​(p.Ala299Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NR5A2 NM_205860.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.52
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32440627).

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.896C>T	p.Ala299Val	missense	Exon 5 of 8	NP_995582.1	O00482-1
	NR5A2	NM_003822.5		c.758C>T	p.Ala253Val	missense	Exon 4 of 7	NP_003813.1	F1D8R9
	NR5A2	NM_001276464.2		c.680C>T	p.Ala227Val	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.896C>T	p.Ala299Val	missense	Exon 5 of 8	ENSP00000356331.3	O00482-1
	NR5A2	ENST00000236914.7	TSL:1	c.758C>T	p.Ala253Val	missense	Exon 4 of 7	ENSP00000236914.3	O00482-2
	NR5A2	ENST00000367357.3	TSL:1	c.656C>T	p.Ala219Val	missense	Exon 3 of 4	ENSP00000356326.3	H0Y328

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

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	0.088
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.0	N
PhyloP100		7.5
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.96	N
REVEL	Uncertain	0.35
Sift	Benign	0.12	T
Sift4G	Benign	0.15	T
Polyphen		0.077	B
Vest4		0.44
MutPred		0.25		Gain of catalytic residue at A299 (P = 0.0451)
MVP		0.51
MPC		0.46
ClinPred		0.69	D
GERP RS		5.3
Varity_R		0.42
gMVP		0.54
Mutation Taster		=56/44	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr1-200017732;