NDRG4 p.Val119Leu

Variant names:

• chr16-58504632-G-T
• NM_001242835.2:c.355G>T
• NDRG4 p.Val119Leu

Your query was ambiguous. Multiple possible variants found:

• chr16-58504632-G-T
• chr16-58504632-G-C
• chr16-58504632-GTG-TTA
• chr16-58504632-GTG-CTT
• chr16-58504632-GTG-CTC
• chr16-58504632-GTG-CTA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001242835.2(NDRG4):​c.355G>T​(p.Val119Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NDRG4 NM_001242835.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.14
• Publications: 0 publications found

Genes affected

NDRG4 (HGNC:14466): (NDRG family member 4) 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 that is required for cell cycle progression and survival in primary astrocytes and may be involved in the regulation of mitogenic signalling in vascular smooth muscles cells. Alternative splicing results in multiple transcripts encoding different isoforms.[provided by RefSeq, Jun 2011]

NDRG4 Gene-Disease associations (from GenCC):

• achromatopsia

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242835.2. 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
	NDRG4	NM_001242835.2	MANE Select	c.355G>T	p.Val119Leu	missense	Exon 5 of 15	NP_001229764.1	A0A0S2Z5R7
	NDRG4	NM_001378332.1		c.601G>T	p.Val201Leu	missense	Exon 8 of 18	NP_001365261.1
	NDRG4	NM_001378333.1		c.565G>T	p.Val189Leu	missense	Exon 7 of 17	NP_001365262.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDRG4	ENST00000570248.6	TSL:1 MANE Select	c.355G>T	p.Val119Leu	missense	Exon 5 of 15	ENSP00000457659.1	Q9ULP0-1
	NDRG4	ENST00000394282.8	TSL:1	c.511G>T	p.Val171Leu	missense	Exon 7 of 16	ENSP00000377823.4	Q9ULP0-6
	NDRG4	ENST00000258187.9	TSL:1	c.451G>T	p.Val151Leu	missense	Exon 7 of 16	ENSP00000258187.5	Q9ULP0-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Benign	0.0016	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.025	T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.086	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		5.1
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.6	N
REVEL	Pathogenic	0.70
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.075	T
Varity_R		0.37
gMVP		0.79

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-58538536;