rs6075337

chr20-18412668-C-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.1485G>C(p.Leu495=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.761 in 1,612,512 control chromosomes in the GnomAD database, including 474,713 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 0.71 (39272 hom., cov: 31)
  • Exomes 𝑓: 0.77 (435441 hom.)
• Consequence: DZANK1 NM_001367614.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.921

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=-0.63).
• BP7: Synonymous conserved (PhyloP=0.921 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DZANK1	NM_001367614.1	c.1485G>C	p.Leu495=	synonymous_variant	13/21	ENST00000699568.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DZANK1	ENST00000699568.1	c.1485G>C	p.Leu495=	synonymous_variant	13/21		NM_001367614.1	P2

Frequencies

GnomAD3 genomes AF: 0.711 AC: 107991 AN: 151890 Hom.: 39250 Cov.: 31

Gnomad AFR AF: 0.641

Gnomad AMI AF: 0.788

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.763

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.807

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.736

Gnomad NFE AF: 0.784

Gnomad OTH AF: 0.728

GnomAD3 exomes AF: 0.707 AC: 176076 AN: 248968 Hom.: 64999 AF XY: 0.724 AC XY: 97818 AN XY: 135068

Gnomad AFR exome AF: 0.638

Gnomad AMR exome AF: 0.550

Gnomad ASJ exome AF: 0.778

Gnomad EAS exome AF: 0.287

Gnomad SAS exome AF: 0.829

Gnomad FIN exome AF: 0.754

Gnomad NFE exome AF: 0.782

Gnomad OTH exome AF: 0.736

GnomAD4 exome AF: 0.767 AC: 1119670 AN: 1460502 Hom.: 435441 Cov.: 60 AF XY: 0.770 AC XY: 559346 AN XY: 726554

Gnomad4 AFR exome AF: 0.639

Gnomad4 AMR exome AF: 0.563

Gnomad4 ASJ exome AF: 0.776

Gnomad4 EAS exome AF: 0.334

Gnomad4 SAS exome AF: 0.828

Gnomad4 FIN exome AF: 0.752

Gnomad4 NFE exome AF: 0.791

Gnomad4 OTH exome AF: 0.748

GnomAD4 genome AF: 0.711 AC: 108056 AN: 152010 Hom.: 39272 Cov.: 31 AF XY: 0.707 AC XY: 52529 AN XY: 74272

Gnomad4 AFR AF: 0.641

Gnomad4 AMR AF: 0.634

Gnomad4 ASJ AF: 0.763

Gnomad4 EAS AF: 0.315

Gnomad4 SAS AF: 0.807

Gnomad4 FIN AF: 0.749

Gnomad4 NFE AF: 0.784

Gnomad4 OTH AF: 0.729

Alfa AF: 0.766 Hom.: 14539

Bravo AF: 0.694

Asia WGS AF: 0.570 AC: 1986 AN: 3478

EpiCase AF: 0.785

EpiControl AF: 0.782

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	4.2
Dann	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs6075337; hg19: chr20-18393312; COSMIC: COSV52749007; COSMIC: COSV52749007;