rs6075337

Variant names:

• chr20-18412668-C-G
• rs6075337
• NM_001367614.1:c.1485G>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001367614.1(DZANK1):​c.1485G>C​(p.Leu495Leu) 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
• Publications: 23 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DZANK1	NM_001367614.1	c.1485G>C	p.Leu495Leu	synonymous_variant	Exon 13 of 21	ENST00000699568.1	NP_001354543.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DZANK1	ENST00000699568.1	c.1485G>C	p.Leu495Leu	synonymous_variant	Exon 13 of 21		NM_001367614.1	ENSP00000514442.1
DZANK1	ENST00000699590.1	c.1443G>C	p.Leu481Leu	synonymous_variant	Exon 13 of 21			ENSP00000514461.1
DZANK1	ENST00000699525.1	c.1428G>C	p.Leu476Leu	synonymous_variant	Exon 13 of 21			ENSP00000514418.1
DZANK1	ENST00000357236.8	c.831G>C	p.Leu277Leu	synonymous_variant	Exon 9 of 17	5		ENSP00000349774.5
DZANK1	ENST00000480488.2	c.24G>C	p.Leu8Leu	synonymous_variant	Exon 2 of 6	5		ENSP00000484666.1
DZANK1	ENST00000377630.9	n.*616G>C		non_coding_transcript_exon_variant	Exon 12 of 20	2		ENSP00000366857.6
DZANK1	ENST00000460891.5	n.*1873G>C		non_coding_transcript_exon_variant	Exon 13 of 14	2		ENSP00000477872.1
DZANK1	ENST00000377630.9	n.*616G>C		3_prime_UTR_variant	Exon 12 of 20	2		ENSP00000366857.6
DZANK1	ENST00000460891.5	n.*1873G>C		3_prime_UTR_variant	Exon 13 of 14	2		ENSP00000477872.1

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

GnomAD2 exomes AF: 0.707 AC: 176076 AN: 248968 AF XY: 0.724

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 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

African (AFR) AF: 0.639 AC: 21372 AN: 33436

American (AMR) AF: 0.563 AC: 25165 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.776 AC: 20267 AN: 26128

East Asian (EAS) AF: 0.334 AC: 13275 AN: 39700

South Asian (SAS) AF: 0.828 AC: 71370 AN: 86212

European-Finnish (FIN) AF: 0.752 AC: 40159 AN: 53402

Middle Eastern (MID) AF: 0.774 AC: 3946 AN: 5096

European-Non Finnish (NFE) AF: 0.791 AC: 879049 AN: 1111544

Other (OTH) AF: 0.748 AC: 45067 AN: 60268

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

African (AFR) AF: 0.641 AC: 26538 AN: 41430

American (AMR) AF: 0.634 AC: 9700 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.763 AC: 2646 AN: 3470

East Asian (EAS) AF: 0.315 AC: 1624 AN: 5152

South Asian (SAS) AF: 0.807 AC: 3881 AN: 4810

European-Finnish (FIN) AF: 0.749 AC: 7913 AN: 10560

Middle Eastern (MID) AF: 0.733 AC: 214 AN: 292

European-Non Finnish (NFE) AF: 0.784 AC: 53282 AN: 67982

Other (OTH) AF: 0.729 AC: 1539 AN: 2112

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
PhyloP100		0.92
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6075337; hg19: chr20-18393312; COSMIC: COSV52749007; COSMIC: COSV52749007;