chr20-18465319-A-G

Variant names:

• chr20-18465319-A-G
• rs6035051
• NM_001367614.1:c.40T>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.40T>C​(p.Leu14Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 1,606,564 control chromosomes in the GnomAD database, including 252,319 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 0.57 (25006 hom., cov: 30)
  • Exomes 𝑓: 0.56 (227313 hom.)
• Consequence: DZANK1 NM_001367614.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.69
• Publications: 28 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=-0.58).
• BP7: Synonymous conserved (PhyloP=2.69 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DZANK1	NM_001367614.1	c.40T>C	p.Leu14Leu	synonymous_variant	Exon 2 of 21	ENST00000699568.1	NP_001354543.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DZANK1	ENST00000699568.1	c.40T>C	p.Leu14Leu	synonymous_variant	Exon 2 of 21		NM_001367614.1	ENSP00000514442.1
DZANK1	ENST00000699590.1	c.40T>C	p.Leu14Leu	synonymous_variant	Exon 2 of 21			ENSP00000514461.1
DZANK1	ENST00000699525.1	c.40T>C	p.Leu14Leu	synonymous_variant	Exon 2 of 21			ENSP00000514418.1
DZANK1	ENST00000377630.9	n.40T>C		non_coding_transcript_exon_variant	Exon 2 of 20	2		ENSP00000366857.6
DZANK1	ENST00000460891.5	n.40T>C		non_coding_transcript_exon_variant	Exon 2 of 14	2		ENSP00000477872.1

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86825 AN: 151790 Hom.: 24993 Cov.: 30

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.524

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.562

Gnomad OTH AF: 0.538

GnomAD2 exomes AF: 0.564 AC: 137690 AN: 244324 AF XY: 0.559

Gnomad AFR exome AF: 0.586

Gnomad AMR exome AF: 0.586

Gnomad ASJ exome AF: 0.547

Gnomad EAS exome AF: 0.611

Gnomad FIN exome AF: 0.563

Gnomad NFE exome AF: 0.564

Gnomad OTH exome AF: 0.558

GnomAD4 exome AF: 0.558 AC: 811040 AN: 1454656 Hom.: 227313 Cov.: 32 AF XY: 0.556 AC XY: 402160 AN XY: 723476

African (AFR) AF: 0.589 AC: 19590 AN: 33248

American (AMR) AF: 0.584 AC: 25815 AN: 44208

Ashkenazi Jewish (ASJ) AF: 0.545 AC: 14145 AN: 25974

East Asian (EAS) AF: 0.534 AC: 21089 AN: 39510

South Asian (SAS) AF: 0.506 AC: 43245 AN: 85504

European-Finnish (FIN) AF: 0.571 AC: 30351 AN: 53110

Middle Eastern (MID) AF: 0.522 AC: 3000 AN: 5748

European-Non Finnish (NFE) AF: 0.560 AC: 620452 AN: 1107204

Other (OTH) AF: 0.554 AC: 33353 AN: 60150

GnomAD4 genome AF: 0.572 AC: 86876 AN: 151908 Hom.: 25006 Cov.: 30 AF XY: 0.573 AC XY: 42503 AN XY: 74226

African (AFR) AF: 0.590 AC: 24410 AN: 41406

American (AMR) AF: 0.599 AC: 9145 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 1911 AN: 3472

East Asian (EAS) AF: 0.590 AC: 3042 AN: 5156

South Asian (SAS) AF: 0.524 AC: 2523 AN: 4812

European-Finnish (FIN) AF: 0.561 AC: 5897 AN: 10512

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.562 AC: 38200 AN: 67978

Other (OTH) AF: 0.534 AC: 1124 AN: 2106

Alfa AF: 0.565 Hom.: 52589

Bravo AF: 0.576

Asia WGS AF: 0.538 AC: 1869 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	10
DANN	Benign	0.81
PhyloP100		2.7
PromoterAI		0.029	Neutral
Mutation Taster		=291/9	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs6035051; hg19: chr20-18445963; COSMIC: COSV52747590; COSMIC: COSV52747590;