rs774872040

Variant names:

• chr1-200048760-A-T
• rs774872040
• NM_205860.3:c.1052A>T
• NR5A2 p.Gln351Leu

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 3P and 5B. PM2 PP3 BP6 BS2

The NM_205860.3(NR5A2):​c.1052A>T​(p.Gln351Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,890 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 Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: NR5A2 NM_205860.3 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 7.06
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.827
• BP6: Variant 1-200048760-A-T is Benign according to our data. Variant chr1-200048760-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 207916.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAdExome4 at 5 AD gene.

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.1052A>T	p.Gln351Leu	missense	Exon 5 of 8	NP_995582.1	O00482-1
	NR5A2	NM_003822.5		c.914A>T	p.Gln305Leu	missense	Exon 4 of 7	NP_003813.1	F1D8R9
	NR5A2	NM_001276464.2		c.836A>T	p.Gln279Leu	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.1052A>T	p.Gln351Leu	missense	Exon 5 of 8	ENSP00000356331.3	O00482-1
	NR5A2	ENST00000236914.7	TSL:1	c.914A>T	p.Gln305Leu	missense	Exon 4 of 7	ENSP00000236914.3	O00482-2
	NR5A2	ENST00000367357.3	TSL:1	c.812A>T	p.Gln271Leu	missense	Exon 3 of 4	ENSP00000356326.3	H0Y328

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000795 AC: 2 AN: 251476 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461890 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 727246

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: 0.000126 AC: 5 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: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	Long QT syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.50
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.93	D
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.82	T
M_CAP	Pathogenic	0.57	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Pathogenic	3.0	M
PhyloP100		7.1
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-5.9	D
REVEL	Pathogenic	0.83
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.0030	D
Varity_R		0.87
gMVP		0.67
Mutation Taster		=5/95	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs774872040;

hg19: chr1-200017888;

COSMIC: COSV52648337;

COSMIC: COSV52648337;