chr20-18433712-A-G

Variant names:

• chr20-18433712-A-G
• rs6035042
• NM_001367614.1:c.858T>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001367614.1(DZANK1):​c.858T>C​(p.Cys286Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.878 in 1,613,874 control chromosomes in the GnomAD database, including 623,897 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.83 (52882 hom., cov: 34)
  • Exomes 𝑓: 0.88 (571015 hom.)
• Consequence: DZANK1 NM_001367614.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.821
• Publications: 25 publications found

Genes affected

DZANK1 (HGNC:15858): (double zinc ribbon and ankyrin repeat domains 1) This gene contains two ankyrin repeat-encoding regions. Ankyrin repeats are tandemly repeated modules of about 33 amino acids described as L-shaped structures consisting of a beta-hairpin and two alpha-helices. Ankyrin repeats occur in a large number of functionally diverse proteins, mainly from eukaryotes, and are known to function as protein-protein interaction domains. [provided by RefSeq, Dec 2018]

RNA5SP476 (HGNC:43376): (RNA, 5S ribosomal pseudogene 476)

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.15).
• BP7: Synonymous conserved (PhyloP=0.821 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367614.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DZANK1	NM_001367614.1	MANE Select	c.858T>C	p.Cys286Cys	synonymous	Exon 9 of 21	NP_001354543.1
	DZANK1	NM_001367617.1		c.858T>C	p.Cys286Cys	synonymous	Exon 9 of 21	NP_001354546.1
	DZANK1	NM_001367618.1		c.858T>C	p.Cys286Cys	synonymous	Exon 9 of 21	NP_001354547.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DZANK1	ENST00000699568.1	MANE Select	c.858T>C	p.Cys286Cys	synonymous	Exon 9 of 21	ENSP00000514442.1
	DZANK1	ENST00000699590.1		c.816T>C	p.Cys272Cys	synonymous	Exon 9 of 21	ENSP00000514461.1
	DZANK1	ENST00000699525.1		c.801T>C	p.Cys267Cys	synonymous	Exon 9 of 21	ENSP00000514418.1

Frequencies

GnomAD3 genomes AF: 0.830 AC: 126204 AN: 152140 Hom.: 52834 Cov.: 34

Gnomad AFR AF: 0.720

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.801

Gnomad ASJ AF: 0.838

Gnomad EAS AF: 0.850

Gnomad SAS AF: 0.959

Gnomad FIN AF: 0.879

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.883

Gnomad OTH AF: 0.837

GnomAD2 exomes AF: 0.862 AC: 214844 AN: 249188 AF XY: 0.871

Gnomad AFR exome AF: 0.715

Gnomad AMR exome AF: 0.788

Gnomad ASJ exome AF: 0.856

Gnomad EAS exome AF: 0.836

Gnomad FIN exome AF: 0.880

Gnomad NFE exome AF: 0.881

Gnomad OTH exome AF: 0.869

GnomAD4 exome AF: 0.883 AC: 1290539 AN: 1461616 Hom.: 571015 Cov.: 60 AF XY: 0.886 AC XY: 644068 AN XY: 727098

African (AFR) AF: 0.716 AC: 23964 AN: 33476

American (AMR) AF: 0.791 AC: 35369 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.851 AC: 22250 AN: 26136

East Asian (EAS) AF: 0.860 AC: 34141 AN: 39698

South Asian (SAS) AF: 0.956 AC: 82426 AN: 86256

European-Finnish (FIN) AF: 0.879 AC: 46917 AN: 53386

Middle Eastern (MID) AF: 0.859 AC: 4954 AN: 5768

European-Non Finnish (NFE) AF: 0.888 AC: 987555 AN: 1111808

Other (OTH) AF: 0.877 AC: 52963 AN: 60374

GnomAD4 genome AF: 0.830 AC: 126305 AN: 152258 Hom.: 52882 Cov.: 34 AF XY: 0.831 AC XY: 61861 AN XY: 74452

African (AFR) AF: 0.720 AC: 29925 AN: 41536

American (AMR) AF: 0.802 AC: 12259 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.838 AC: 2911 AN: 3472

East Asian (EAS) AF: 0.850 AC: 4403 AN: 5182

South Asian (SAS) AF: 0.959 AC: 4630 AN: 4826

European-Finnish (FIN) AF: 0.879 AC: 9318 AN: 10600

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.883 AC: 60071 AN: 68028

Other (OTH) AF: 0.839 AC: 1774 AN: 2114

Alfa AF: 0.865 Hom.: 239409

Bravo AF: 0.816

Asia WGS AF: 0.887 AC: 3084 AN: 3478

EpiCase AF: 0.879

EpiControl AF: 0.875

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_noAF	Benign	-0.62
CADD	Benign	1.2
DANN	Benign	0.63
PhyloP100		0.82
PromoterAI		0.025	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs6035042; hg19: chr20-18414356; COSMIC: COSV52750610; COSMIC: COSV52750610;