rs138839833

Positions:

• chr8-133250525-C-G
• chr8-133250525-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006096.4(NDRG1):​c.613G>C​(p.Val205Leu) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: NDRG1 NM_006096.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.56

Genes affected

NDRG1 (HGNC:7679): (N-myc downstream regulated 1) This gene is a member of the N-myc downregulated gene family which belongs to the alpha/beta hydrolase superfamily. The protein encoded by this gene is a cytoplasmic protein involved in stress responses, hormone responses, cell growth, and differentiation. The encoded protein is necessary for p53-mediated caspase activation and apoptosis. Mutations in this gene are a cause of Charcot-Marie-Tooth disease type 4D, and expression of this gene may be a prognostic indicator for several types of cancer. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]

ACMG classification

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=0.06266177).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDRG1	NM_006096.4	c.613G>C	p.Val205Leu	missense_variant	10/16	ENST00000323851.13	NP_006087.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDRG1	ENST00000323851.13	c.613G>C	p.Val205Leu	missense_variant	10/16	1	NM_006096.4	ENSP00000319977	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	18
DANN	Benign	0.27
DEOGEN2	Benign	0.061	T;.;T;.
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.67	.;T;T;T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.063	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.49	N;.;N;.
MutationTaster	Benign	1.0	D;D;N;N;N;N;N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	0.020	N;N;N;N
REVEL	Benign	0.025
Sift	Benign	0.93	T;T;T;T
Sift4G	Benign	0.35	T;T;T;T
Polyphen		0.012	B;.;B;.
Vest4		0.26
MutPred		0.27		Gain of helix (P = 0.132);.;Gain of helix (P = 0.132);.;
MVP		0.37
MPC		0.30
ClinPred		0.21	T
GERP RS		2.5
Varity_R		0.033
gMVP		0.47

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

LitVar

Other links and lift over

dbSNP: rs138839833; hg19: chr8-134262768;