20-18433712-A-G

Position:

• chr20-18433712-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001367614.1(DZANK1):​c.858T>C​(p.Cys286=) 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

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DZANK1	NM_001367614.1	c.858T>C	p.Cys286=	synonymous_variant	9/21	ENST00000699568.1	NP_001354543.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DZANK1	ENST00000699568.1	c.858T>C	p.Cys286=	synonymous_variant	9/21		NM_001367614.1	ENSP00000514442	P2

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

GnomAD3 exomes AF: 0.862 AC: 214844 AN: 249188 Hom.: 93115 AF XY: 0.871 AC XY: 117752 AN XY: 135190

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 SAS exome AF: 0.956

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

Gnomad4 AFR exome AF: 0.716

Gnomad4 AMR exome AF: 0.791

Gnomad4 ASJ exome AF: 0.851

Gnomad4 EAS exome AF: 0.860

Gnomad4 SAS exome AF: 0.956

Gnomad4 FIN exome AF: 0.879

Gnomad4 NFE exome AF: 0.888

Gnomad4 OTH exome AF: 0.877

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

Gnomad4 AFR AF: 0.720

Gnomad4 AMR AF: 0.802

Gnomad4 ASJ AF: 0.838

Gnomad4 EAS AF: 0.850

Gnomad4 SAS AF: 0.959

Gnomad4 FIN AF: 0.879

Gnomad4 NFE AF: 0.883

Gnomad4 OTH AF: 0.839

Alfa AF: 0.872 Hom.: 131711

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	1.2
DANN	Benign	0.63

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

Publications

LitVar

Other links and lift over

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