rs374483147

Variant names:

• chr20-36660368-C-A
• rs374483147
• NM_032013.4:c.827G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-36660368-C-A
• chr20-36660368-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_032013.4(NDRG3):​c.827G>T​(p.Arg276Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,453,736 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. R276H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NDRG3 NM_032013.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.28
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.771

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDRG3	NM_032013.4	MANE Select	c.827G>T	p.Arg276Leu	missense	Exon 13 of 16	NP_114402.1	Q9UGV2-1
	NDRG3	NM_022477.4		c.791G>T	p.Arg264Leu	missense	Exon 12 of 15	NP_071922.2
	NDRG3	NR_038370.2		n.694G>T		non_coding_transcript_exon	Exon 11 of 14

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDRG3	ENST00000349004.6	TSL:1 MANE Select	c.827G>T	p.Arg276Leu	missense	Exon 13 of 16	ENSP00000345292.1	Q9UGV2-1
	NDRG3	ENST00000359675.6	TSL:1	c.791G>T	p.Arg264Leu	missense	Exon 12 of 15	ENSP00000352703.2	Q9UGV2-2
	NDRG3	ENST00000373773.7	TSL:1	c.542G>T	p.Arg181Leu	missense	Exon 10 of 13	ENSP00000362878.3	F8WBF9

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1453736 Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1 AN XY: 723312

African (AFR) AF: 0.00 AC: 0 AN: 33118

American (AMR) AF: 0.00 AC: 0 AN: 44348

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25864

East Asian (EAS) AF: 0.0000255 AC: 1 AN: 39236

South Asian (SAS) AF: 0.00 AC: 0 AN: 85748

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53042

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1106820

Other (OTH) AF: 0.00 AC: 0 AN: 59870

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Uncertain	0.051	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.029	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.024	T
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		4.3
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.28
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.93	P
Vest4		0.82
MutPred		0.68		Gain of helix (P = 0.132)
MVP		0.39
MPC		1.0
ClinPred		1.0	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.74
gMVP		0.74
Mutation Taster		=40/60	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs374483147; hg19: chr20-35288771;