chr8-133284281-C-A

Variant names:

• chr8-133284281-C-A
• NM_006096.4:c.31G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006096.4(NDRG1):​c.31G>T​(p.Ala11Ser) 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. 12/21 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: 33)
• Consequence: NDRG1 NM_006096.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.33

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23754147).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDRG1	NM_006096.4	c.31G>T	p.Ala11Ser	missense_variant	Exon 2 of 16	ENST00000323851.13	NP_006087.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDRG1	ENST00000323851.13	c.31G>T	p.Ala11Ser	missense_variant	Exon 2 of 16	1	NM_006096.4	ENSP00000319977.8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;T;T;T;.;T;.;.;T;.;T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.86	.;D;T;T;D;D;.;D;D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.24	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;L;.;.;.;.;.;.;.;.;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.090	N;N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.090
Sift	Uncertain	0.015	D;D;D;D;T;D;D;D;T;D;D
Sift4G	Uncertain	0.021	D;D;D;D;.;D;D;D;.;.;T
Polyphen		0.67	P;P;D;.;.;.;.;.;.;.;.
Vest4		0.39
MutPred		0.35		Gain of disorder (P = 0.0102);Gain of disorder (P = 0.0102);Gain of disorder (P = 0.0102);Gain of disorder (P = 0.0102);.;Gain of disorder (P = 0.0102);Gain of disorder (P = 0.0102);Gain of disorder (P = 0.0102);.;Gain of disorder (P = 0.0102);.;
MVP		0.51
MPC		0.29
ClinPred		0.78	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.37

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-134296524;