Genetic Variant NDRG3:p.Arg326Gln (chr20-36653671-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_032013.4(NDRG3):c.977G>A(p.Arg326Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,490 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

NDRG3
NM_032013.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.34

Publications

0 publications found

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]

NDRG3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36086243).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032013.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NDRG3	NM_032013.4	MANE Select	c.977G>A	p.Arg326Gln	missense	Exon 16 of 16	NP_114402.1	Q9UGV2-1
NDRG3	NM_022477.4		c.941G>A	p.Arg314Gln	missense	Exon 15 of 15	NP_071922.2
NDRG3	NR_038370.2		n.844G>A		non_coding_transcript_exon	Exon 14 of 14

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NDRG3	ENST00000349004.6	TSL:1 MANE Select	c.977G>A	p.Arg326Gln	missense	Exon 16 of 16	ENSP00000345292.1	Q9UGV2-1
NDRG3	ENST00000359675.6	TSL:1	c.941G>A	p.Arg314Gln	missense	Exon 15 of 15	ENSP00000352703.2	Q9UGV2-2
NDRG3	ENST00000373773.7	TSL:1	c.692G>A	p.Arg231Gln	missense	Exon 13 of 13	ENSP00000362878.3	F8WBF9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000199

AC:

AN:

250682

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0000470

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461490

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727048

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53094

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.00000540

AC:

AN:

1111996

Other (OTH)

AF:

0.00

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.059

MetaRNN

Benign

0.36

MetaSVM

Benign

-0.37

MutationAssessor

Uncertain

2.9

PhyloP100

7.3

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.20

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0040

Polyphen

0.057

Vest4

0.39

MutPred

0.50

Loss of sheet (P = 0.0084)

MVP

0.71

MPC

1.0

ClinPred

0.93

GERP RS

4.7

Varity_R

0.58

gMVP

0.53

Mutation Taster

=60/40

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over