chr16-58494832-T-TAAA

Variant names:

• chr16-58494832-T-TAAA
• rs59711785
• ENST00000394282.8:c.133-132_133-131insAAA

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001378332.1(NDRG4):​c.133-119_133-117dupAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.071 in 404,254 control chromosomes in the GnomAD database, including 6 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (19 hom., cov: 0)
  • Exomes 𝑓: 0.071 (6 hom.)
  • Failed GnomAD Quality Control
• Consequence: NDRG4 NM_001378332.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.525
• 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: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 16-58494832-T-TAAA is Benign according to our data. Variant chr16-58494832-T-TAAA is described in ClinVar as Likely_benign. ClinVar VariationId is 1316963.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 6 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDRG4	NM_001378332.1		c.133-119_133-117dupAAA		intron	N/A	NP_001365261.1
	NDRG4	NM_001378333.1		c.133-119_133-117dupAAA		intron	N/A	NP_001365262.1
	NDRG4	NM_001378334.1		c.133-119_133-117dupAAA		intron	N/A	NP_001365263.1

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.0117 AC: 1581 AN: 134962 Hom.: 18 Cov.: 0

Gnomad AFR AF: 0.0300

Gnomad AMI AF: 0.0321

Gnomad AMR AF: 0.00772

Gnomad ASJ AF: 0.00332

Gnomad EAS AF: 0.00813

Gnomad SAS AF: 0.0101

Gnomad FIN AF: 0.00287

Gnomad MID AF: 0.00355

Gnomad NFE AF: 0.00368

Gnomad OTH AF: 0.0100

GnomAD4 exome AF: 0.0710 AC: 28714 AN: 404254 Hom.: 6 AF XY: 0.0703 AC XY: 14849 AN XY: 211314

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

African (AFR) AF: 0.0986 AC: 1058 AN: 10730

American (AMR) AF: 0.0830 AC: 1356 AN: 16342

Ashkenazi Jewish (ASJ) AF: 0.0679 AC: 766 AN: 11288

East Asian (EAS) AF: 0.0665 AC: 1784 AN: 26828

South Asian (SAS) AF: 0.0579 AC: 2022 AN: 34930

European-Finnish (FIN) AF: 0.0670 AC: 1647 AN: 24564

Middle Eastern (MID) AF: 0.0564 AC: 115 AN: 2038

European-Non Finnish (NFE) AF: 0.0718 AC: 18351 AN: 255704

Other (OTH) AF: 0.0740 AC: 1615 AN: 21830

⚠️ 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.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0117 AC: 1583 AN: 134940 Hom.: 19 Cov.: 0 AF XY: 0.0118 AC XY: 762 AN XY: 64332

African (AFR) AF: 0.0300 AC: 1088 AN: 36312

American (AMR) AF: 0.00772 AC: 104 AN: 13476

Ashkenazi Jewish (ASJ) AF: 0.00332 AC: 11 AN: 3318

East Asian (EAS) AF: 0.00816 AC: 38 AN: 4656

South Asian (SAS) AF: 0.0102 AC: 41 AN: 4016

European-Finnish (FIN) AF: 0.00287 AC: 19 AN: 6626

Middle Eastern (MID) AF: 0.00391 AC: 1 AN: 256

European-Non Finnish (NFE) AF: 0.00366 AC: 233 AN: 63602

Other (OTH) AF: 0.0111 AC: 20 AN: 1806

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.53
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs59711785; hg19: chr16-58528736;