rs2233318

Variant names:

• chr8-133264630-T-A
• rs2233318
• ENST00000522476.5:c.-77A>T

Your query was ambiguous. Multiple possible variants found:

• chr8-133264630-T-A
• chr8-133264630-T-C
• chr8-133264630-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000522476.5(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 ENST00000522476.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.08
• Publications: 0 publications found

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: Orphanet, Labcorp Genetics (formerly Invitae), Illumina

ACMG classification

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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDRG1	NM_006096.4	c.122A>T	p.His41Leu	missense_variant	Exon 4 of 16	ENST00000323851.13	NP_006087.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDRG1	ENST00000323851.13	c.122A>T	p.His41Leu	missense_variant	Exon 4 of 16	1	NM_006096.4	ENSP00000319977.8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.27	T;T;.;T;.;.;T;.;T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.28
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.81	.;T;T;T;.;T;T;T;T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.39	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;M;.;.;.;.;.;.;.
PhyloP100		3.1
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-4.7	D;D;D;D;D;D;D;D;D
REVEL	Benign	0.12
Sift	Benign	0.043	D;D;T;D;T;T;T;D;D
Sift4G	Benign	0.13	T;T;.;T;T;T;.;.;T
Polyphen		0.098	B;B;.;.;.;.;.;.;.
Vest4		0.62
MutPred		0.55		Loss of disorder (P = 0.0466);Loss of disorder (P = 0.0466);.;Loss of disorder (P = 0.0466);Loss of disorder (P = 0.0466);Loss of disorder (P = 0.0466);.;Loss of disorder (P = 0.0466);.;
MVP		0.42
MPC		0.39
ClinPred		0.94	D
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

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

Other links and lift over

dbSNP: rs2233318; hg19: chr8-134276873;