Genetic Variant NDRG4:c.133-132_133-131insAAAAAAA (chr16-58494832-T-TAAAAAAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001378332.1(NDRG4):c.133-123_133-117dupAAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000022 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000046 ( 0 hom. )

Failed GnomAD Quality Control

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 0 ACMG points.

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.133-123_133-117dupAAAAAAA	intron	N/A	NP_001365261.1
NDRG4	NM_001378333.1	c.133-123_133-117dupAAAAAAA	intron	N/A	NP_001365262.1
NDRG4	NM_001378334.1	c.133-123_133-117dupAAAAAAA	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_133-131insAAAAAAA	intron	N/A	ENSP00000377823.4	Q9ULP0-6
NDRG4	ENST00000258187.9	TSL:1	c.73-132_73-131insAAAAAAA	intron	N/A	ENSP00000258187.5	Q9ULP0-3
NDRG4	ENST00000394279.6	TSL:5	c.73-132_73-131insAAAAAAA	intron	N/A	ENSP00000377820.2	Q9ULP0-3

Frequencies

GnomAD3 genomes

AF:

0.0000222

AC:

AN:

135034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000276

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:

0.0000157

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000464

AC:

AN:

409352

Hom.:

AF XY:

0.0000327

AC XY:

AN XY:

213990

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

10938

American (AMR)

AF:

0.00

AC:

AN:

16578

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11436

East Asian (EAS)

AF:

0.000368

AC:

AN:

27198

South Asian (SAS)

AF:

0.00

AC:

AN:

35316

European-Finnish (FIN)

AF:

0.00

AC:

AN:

24888

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2062

European-Non Finnish (NFE)

AF:

0.0000348

AC:

AN:

258820

Other (OTH)

AF:

0.00

AC:

AN:

22116

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000781876), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.336

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000222

AC:

AN:

135012

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

64378

show subpopulations

African (AFR)

AF:

0.0000275

AC:

AN:

36332

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:

6632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

258

European-Non Finnish (NFE)

AF:

0.0000157

AC:

AN:

63636

Other (OTH)

AF:

0.00

AC:

AN:

1808

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

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16-58494832-TAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over