chr20-36660368-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032013.4(NDRG3):​c.827G>A​(p.Arg276His) variant causes a missense change. The variant allele was found at a frequency of 0.0000623 in 1,605,260 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

NDRG3
NM_032013.4 missense

Scores

2
10
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.28
Variant links:
Genes affected
NDRG3 (HGNC:14462): (NDRG family member 3) Predicted to be involved in signal transduction. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NDRG3NM_032013.4 linkc.827G>A p.Arg276His missense_variant Exon 13 of 16 ENST00000349004.6 NP_114402.1 Q9UGV2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NDRG3ENST00000349004.6 linkc.827G>A p.Arg276His missense_variant Exon 13 of 16 1 NM_032013.4 ENSP00000345292.1 Q9UGV2-1
NDRG3ENST00000359675.6 linkc.791G>A p.Arg264His missense_variant Exon 12 of 15 1 ENSP00000352703.2 Q9UGV2-2
NDRG3ENST00000373773.7 linkc.542G>A p.Arg181His missense_variant Exon 10 of 13 1 ENSP00000362878.3 F8WBF9
NDRG3ENST00000373803.6 linkc.827G>A p.Arg276His missense_variant Exon 13 of 17 5 ENSP00000362909.2 Q5TH30

Frequencies

GnomAD3 genomes
AF:
0.0000462
AC:
7
AN:
151522
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000243
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000194
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000736
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000722
AC:
18
AN:
249202
Hom.:
0
AF XY:
0.0000519
AC XY:
7
AN XY:
134774
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000590
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000329
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000124
Gnomad OTH exome
AF:
0.000166
GnomAD4 exome
AF:
0.0000640
AC:
93
AN:
1453738
Hom.:
0
Cov.:
28
AF XY:
0.0000608
AC XY:
44
AN XY:
723314
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000451
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000255
Gnomad4 SAS exome
AF:
0.0000117
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000741
Gnomad4 OTH exome
AF:
0.0000668
GnomAD4 genome
AF:
0.0000462
AC:
7
AN:
151522
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
73972
show subpopulations
Gnomad4 AFR
AF:
0.0000243
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000194
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000736
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000386
Hom.:
0
Bravo
AF:
0.0000567
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000247
AC:
3

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 12, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.827G>A (p.R276H) alteration is located in exon 13 (coding exon 12) of the NDRG3 gene. This alteration results from a G to A substitution at nucleotide position 827, causing the arginine (R) at amino acid position 276 to be replaced by a histidine (H). 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
Uncertain
0.43
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.40
CADD
Pathogenic
32
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.025
T;.;T;T
Eigen
Uncertain
0.58
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.91
D;D;D;D
M_CAP
Benign
0.015
T
MetaRNN
Uncertain
0.57
D;D;D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.0
.;.;M;.
PrimateAI
Uncertain
0.63
T
PROVEAN
Uncertain
-2.8
D;D;D;D
REVEL
Benign
0.20
Sift
Uncertain
0.0010
D;D;D;D
Sift4G
Uncertain
0.0030
D;D;D;D
Polyphen
1.0
.;D;D;D
Vest4
0.56
MVP
0.49
MPC
0.48
ClinPred
0.50
D
GERP RS
4.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.64
gMVP
0.60

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs374483147; hg19: chr20-35288771; API