Genetic Variant NDRG1:c.-77A>T (chr8-133264630-T-A) – 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_001258432.2(NDRG1):c.-77A>T variant causes a 5 prime UTR premature start codon gain 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

NDRG1
NM_001258432.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.08

Publications

0 publications found

Variant links:

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]

NDRG1 Gene-Disease associations (from GenCC):

Charcot-Marie-Tooth disease type 4D
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Illumina

NDRG1 links:

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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=0.38923606).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001258432.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NDRG1	NM_006096.4	MANE Select	c.122A>T	p.His41Leu	missense	Exon 4 of 16	NP_006087.2
NDRG1	NM_001258432.2		c.-77A>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 14	NP_001245361.1	Q92597-2
NDRG1	NM_001374847.1		c.-77A>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 15	NP_001361776.1	Q92597-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NDRG1	ENST00000522476.5	TSL:1	c.-77A>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 14	ENSP00000427894.1	Q92597-2
NDRG1	ENST00000323851.13	TSL:1 MANE Select	c.122A>T	p.His41Leu	missense	Exon 4 of 16	ENSP00000319977.8	Q92597-1
NDRG1	ENST00000522476.5	TSL:1	c.-77A>T		5_prime_UTR	Exon 2 of 14	ENSP00000427894.1	Q92597-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.070

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.27

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.28

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.81

M_CAP

Benign

0.026

MetaRNN

Benign

0.39

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

PhyloP100

3.1

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-4.7

REVEL

Benign

0.12

Sift

Benign

0.043

Sift4G

Benign

0.13

Polyphen

0.098

Vest4

0.62

MutPred

0.55

Loss of disorder (P = 0.0466)

MVP

0.42

MPC

0.39

ClinPred

0.94

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.23

gMVP

0.65

Mutation Taster

=85/15

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over