9-124522716-C-T

Variant summary

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

The NM_033334.4(NR6A1):​c.1432G>A​(p.Gly478Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

NR6A1
NM_033334.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.00
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=0.0582138).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NR6A1NM_033334.4 linkc.1432G>A p.Gly478Ser missense_variant Exon 10 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.1432G>A p.Gly478Ser missense_variant Exon 10 of 10 1 NM_033334.4 ENSP00000420267.1 Q15406-1
NR6A1ENST00000373584.7 linkc.1420G>A p.Gly474Ser missense_variant Exon 10 of 10 1 ENSP00000362686.3 Q15406-2
NR6A1ENST00000416460.6 linkc.1417G>A p.Gly473Ser missense_variant Exon 10 of 10 1 ENSP00000413701.2 Q15406-5
NR6A1ENST00000344523.8 linkc.1429G>A p.Gly477Ser missense_variant Exon 10 of 10 5 ENSP00000341135.4 Q15406-4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1428150
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
707322
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 17, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1432G>A (p.G478S) alteration is located in exon 10 (coding exon 10) of the NR6A1 gene. This alteration results from a G to A substitution at nucleotide position 1432, causing the glycine (G) at amino acid position 478 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.072
BayesDel_addAF
Benign
-0.0069
T
BayesDel_noAF
Benign
-0.25
CADD
Benign
16
DANN
Benign
0.85
DEOGEN2
Benign
0.16
T;.;.;.
Eigen
Benign
-0.38
Eigen_PC
Benign
-0.15
FATHMM_MKL
Benign
0.46
N
LIST_S2
Benign
0.81
T;T;T;T
M_CAP
Benign
0.063
D
MetaRNN
Benign
0.058
T;T;T;T
MetaSVM
Benign
-0.68
T
MutationAssessor
Benign
-0.69
N;.;.;.
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-0.050
N;N;N;N
REVEL
Benign
0.23
Sift
Benign
0.69
T;T;T;T
Sift4G
Benign
1.0
T;T;T;T
Polyphen
0.0
B;.;B;.
Vest4
0.035
MutPred
0.14
Gain of phosphorylation at G478 (P = 0.0506);.;.;.;
MVP
0.43
MPC
0.28
ClinPred
0.69
D
GERP RS
3.7
Varity_R
0.054
gMVP
0.31

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.080
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-127284995; API