chr9-124536128-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_033334.4(NR6A1):​c.829G>T​(p.Ala277Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,611,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign 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. A277T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

NR6A1
NM_033334.4 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.01
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.064965546).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NR6A1NM_033334.4 linkc.829G>T p.Ala277Ser 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.829G>T p.Ala277Ser missense_variant Exon 7 of 10 1 NM_033334.4 ENSP00000420267.1 Q15406-1
NR6A1ENST00000373584.7 linkc.817G>T p.Ala273Ser missense_variant Exon 7 of 10 1 ENSP00000362686.3 Q15406-2
NR6A1ENST00000416460.6 linkc.814G>T p.Ala272Ser missense_variant Exon 7 of 10 1 ENSP00000413701.2 Q15406-5
NR6A1ENST00000344523.8 linkc.826G>T p.Ala276Ser missense_variant Exon 7 of 10 5 ENSP00000341135.4 Q15406-4

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152144
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1459624
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
725736
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152144
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74300
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.090
BayesDel_addAF
Benign
-0.061
T
BayesDel_noAF
Benign
-0.33
CADD
Benign
13
DANN
Benign
0.74
DEOGEN2
Benign
0.13
T;.;.;.
Eigen
Benign
-0.77
Eigen_PC
Benign
-0.54
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Benign
0.79
T;T;T;T
M_CAP
Benign
0.072
D
MetaRNN
Benign
0.065
T;T;T;T
MetaSVM
Benign
-0.71
T
MutationAssessor
Benign
-0.69
N;.;.;.
PrimateAI
Benign
0.42
T
PROVEAN
Benign
0.80
N;N;N;N
REVEL
Benign
0.20
Sift
Benign
0.78
T;T;T;T
Sift4G
Benign
0.74
T;T;T;T
Polyphen
0.0040
B;.;B;.
Vest4
0.19
MutPred
0.36
Loss of catalytic residue at A277 (P = 0.0366);.;.;.;
MVP
0.27
MPC
0.26
ClinPred
0.26
T
GERP RS
2.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.039
gMVP
0.29

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs764847595; hg19: chr9-127298407; API