rs777612868

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_033334.4(NR6A1):​c.1063G>C​(p.Asp355His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. D355N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000048 ( 0 hom. )

Consequence

NR6A1
NM_033334.4 missense

Scores

6
8
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.36
Variant links:
Genes affected
NR6A1 (HGNC:7985): (nuclear receptor subfamily 6 group A member 1) This gene encodes an orphan nuclear receptor which is a member of the nuclear hormone receptor family. Its expression pattern suggests that it may be involved in neurogenesis and germ cell development. The protein can homodimerize and bind DNA, but in vivo targets have not been identified. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Jun 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.747

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NR6A1NM_033334.4 linkc.1063G>C p.Asp355His missense_variant Exon 7 of 10 ENST00000487099.7 NP_201591.2 Q15406-1F1D8S0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NR6A1ENST00000487099.7 linkc.1063G>C p.Asp355His missense_variant Exon 7 of 10 1 NM_033334.4 ENSP00000420267.1 Q15406-1
NR6A1ENST00000373584.7 linkc.1051G>C p.Asp351His missense_variant Exon 7 of 10 1 ENSP00000362686.3 Q15406-2
NR6A1ENST00000416460.6 linkc.1048G>C p.Asp350His missense_variant Exon 7 of 10 1 ENSP00000413701.2 Q15406-5
NR6A1ENST00000344523.8 linkc.1060G>C p.Asp354His missense_variant Exon 7 of 10 5 ENSP00000341135.4 Q15406-4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251108
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135682
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461862
Hom.:
0
Cov.:
31
AF XY:
0.00000825
AC XY:
6
AN XY:
727228
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000812
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.26
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.10
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.57
D;.;.;.
Eigen
Uncertain
0.63
Eigen_PC
Uncertain
0.66
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.96
D;D;D;D
M_CAP
Uncertain
0.20
D
MetaRNN
Pathogenic
0.75
D;D;D;D
MetaSVM
Pathogenic
0.87
D
MutationAssessor
Benign
1.6
L;.;.;.
PrimateAI
Pathogenic
0.83
D
PROVEAN
Benign
-0.11
N;N;N;N
REVEL
Pathogenic
0.66
Sift
Uncertain
0.021
D;D;D;D
Sift4G
Benign
0.11
T;T;T;T
Polyphen
0.93
P;.;D;.
Vest4
0.64
MutPred
0.38
Loss of helix (P = 0.0558);.;.;.;
MVP
0.72
MPC
1.0
ClinPred
0.72
D
GERP RS
5.2
Varity_R
0.19
gMVP
0.53

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs777612868; hg19: chr9-127298173; API