Genetic Variant NDRG4:c.133-132_133-131insAAAA (chr16-58494832-T-TAAAA) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001378332.1(NDRG4):c.133-120_133-117dupAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00335 in 542,408 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0044 ( 0 hom. )

Consequence

NDRG4
NM_001378332.1 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.525

Publications

0 publications found

Variant links:

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

NDRG4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

PM2

Variant has high frequency in the AFR (0.00481) population. However there is too low homozygotes in high coverage region: (expected more than 1, got 0).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378332.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
NDRG4	NM_001378332.1	c.133-120_133-117dupAAAA	intron	N/A	NP_001365261.1
NDRG4	NM_001378333.1	c.133-120_133-117dupAAAA	intron	N/A	NP_001365262.1
NDRG4	NM_001378334.1	c.133-120_133-117dupAAAA	intron	N/A	NP_001365263.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NDRG4	ENST00000394282.8	TSL:1	c.133-132_133-131insAAAA	intron	N/A	ENSP00000377823.4	Q9ULP0-6
NDRG4	ENST00000258187.9	TSL:1	c.73-132_73-131insAAAA	intron	N/A	ENSP00000258187.5	Q9ULP0-3
NDRG4	ENST00000394279.6	TSL:5	c.73-132_73-131insAAAA	intron	N/A	ENSP00000377820.2	Q9ULP0-3

Frequencies

GnomAD3 genomes

AF:

0.000148

AC:

AN:

135030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000469

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000214

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000314

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00441

AC:

1796

AN:

407400

Hom.:

AF XY:

0.00437

AC XY:

930

AN XY:

212992

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00598

AC:

AN:

10876

American (AMR)

AF:

0.00449

AC:

AN:

16494

Ashkenazi Jewish (ASJ)

AF:

0.00412

AC:

AN:

11394

East Asian (EAS)

AF:

0.00377

AC:

102

AN:

27056

South Asian (SAS)

AF:

0.00335

AC:

118

AN:

35180

European-Finnish (FIN)

AF:

0.00363

AC:

AN:

24764

Middle Eastern (MID)

AF:

0.00440

AC:

AN:

2046

European-Non Finnish (NFE)

AF:

0.00464

AC:

1195

AN:

257592

Other (OTH)

AF:

0.00436

AC:

AN:

21998

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.267

Heterozygous variant carriers

185

370

556

741

926

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000148

AC:

AN:

135008

Hom.:

Cov.:

AF XY:

0.000155

AC XY:

AN XY:

64376

show subpopulations

African (AFR)

AF:

0.000468

AC:

AN:

36334

American (AMR)

AF:

0.00

AC:

AN:

13478

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3318

East Asian (EAS)

AF:

0.000215

AC:

AN:

4658

South Asian (SAS)

AF:

0.00

AC:

AN:

4020

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

258

European-Non Finnish (NFE)

AF:

0.0000314

AC:

AN:

63634

Other (OTH)

AF:

0.00

AC:

AN:

1808

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.53

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over