Genetic Variant DZANK1:p.Leu14Ile (chr20-18465319-A-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001367614.1(DZANK1):c.40T>A(p.Leu14Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DZANK1
NM_001367614.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.69

Publications

28 publications found

Variant links:

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]

DZANK1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28313893).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DZANK1	NM_001367614.1	MANE Select	c.40T>A	p.Leu14Ile	missense	Exon 2 of 21	NP_001354543.1
DZANK1	NM_001367617.1		c.40T>A	p.Leu14Ile	missense	Exon 2 of 21	NP_001354546.1
DZANK1	NM_001367618.1		c.40T>A	p.Leu14Ile	missense	Exon 2 of 21	NP_001354547.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DZANK1	ENST00000699568.1	MANE Select	c.40T>A	p.Leu14Ile	missense	Exon 2 of 21	ENSP00000514442.1
DZANK1	ENST00000699590.1		c.40T>A	p.Leu14Ile	missense	Exon 2 of 21	ENSP00000514461.1
DZANK1	ENST00000699525.1		c.40T>A	p.Leu14Ile	missense	Exon 2 of 21	ENSP00000514418.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1457894

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725034

African (AFR)

AF:

0.00

AC:

AN:

33356

American (AMR)

AF:

0.00

AC:

AN:

44338

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26026

East Asian (EAS)

AF:

0.00

AC:

AN:

39584

South Asian (SAS)

AF:

0.00

AC:

AN:

85708

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53200

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109664

Other (OTH)

AF:

0.00

AC:

AN:

60254

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.068

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0093

Eigen

Benign

0.16

Eigen_PC

Benign

0.12

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.84

M_CAP

Benign

0.032

MetaRNN

Benign

0.28

MetaSVM

Uncertain

-0.28

MutationAssessor

Benign

1.5

PhyloP100

2.7

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.2

REVEL

Benign

0.17

Sift

Benign

0.19

Sift4G

Benign

0.15

Polyphen

1.0

Vest4

0.13

MutPred

0.30

Loss of catalytic residue at L14 (P = 0.0029)

MVP

0.47

MPC

0.30

ClinPred

0.68

GERP RS

2.1

PromoterAI

0.022

Neutral

(source)

Varity_R

0.077

gMVP

0.32

Mutation Taster

=291/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over