Genetic Variant NDRG4:c.133-132_133-131insAAAAAA (chr16-58494832-T-TAAAAAA) – 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.133-122_133-117dupAAAAAA 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 0.000015 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000039 ( 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.133-122_133-117dupAAAAAA	intron	N/A	NP_001365261.1
NDRG4	NM_001378333.1	c.133-122_133-117dupAAAAAA	intron	N/A	NP_001365262.1
NDRG4	NM_001378334.1	c.133-122_133-117dupAAAAAA	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_133-131insAAAAAA	intron	N/A	ENSP00000377823.4	Q9ULP0-6
NDRG4	ENST00000258187.9	TSL:1	c.73-132_73-131insAAAAAA	intron	N/A	ENSP00000258187.5	Q9ULP0-3
NDRG4	ENST00000394279.6	TSL:5	c.73-132_73-131insAAAAAA	intron	N/A	ENSP00000377820.2	Q9ULP0-3

Frequencies

GnomAD3 genomes

AF:

0.0000148

AC:

AN:

135040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000551

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000391

AC:

AN:

409330

Hom.:

AF XY:

0.0000421

AC XY:

AN XY:

213984

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:

16576

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11436

East Asian (EAS)

AF:

0.0000368

AC:

AN:

27196

South Asian (SAS)

AF:

0.0000566

AC:

AN:

35316

European-Finnish (FIN)

AF:

0.0000402

AC:

AN:

24886

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2062

European-Non Finnish (NFE)

AF:

0.0000386

AC:

AN:

258806

Other (OTH)

AF:

0.0000904

AC:

AN:

22114

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000000252165), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.287

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:

0.0000148

AC:

AN:

135040

Hom.:

Cov.:

AF XY:

0.0000311

AC XY:

AN XY:

64378

show subpopulations

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

African (AFR)

AF:

0.0000551

AC:

AN:

36284

American (AMR)

AF:

0.00

AC:

AN:

13472

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3318

East Asian (EAS)

AF:

0.00

AC:

AN:

4676

South Asian (SAS)

AF:

0.00

AC:

AN:

4050

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

63652

Other (OTH)

AF:

0.00

AC:

AN:

1800

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 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: 0.350

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