20-18412783-C-T

Position:

chr20-18412783-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001367614.1(DZANK1):c.1370G>A(p.Gly457Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000174 in 1,613,800 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

DZANK1
NM_001367614.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.75

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:

DZANK1 (HGNC:):

DZANK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DZANK1	NM_001367614.1 linkuse as main transcript	c.1370G>A	p.Gly457Glu	missense_variant	13/21	ENST00000699568.1	NP_001354543.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DZANK1	ENST00000699568.1 linkuse as main transcript	c.1370G>A	p.Gly457Glu	missense_variant	13/21		NM_001367614.1	ENSP00000514442.1	A0A8V8TNE5
DZANK1	ENST00000699590.1 linkuse as main transcript	c.1328G>A	p.Gly443Glu	missense_variant	13/21			ENSP00000514461.1	A0A8V8TPU7
DZANK1	ENST00000699525.1 linkuse as main transcript	c.1313G>A	p.Gly438Glu	missense_variant	13/21			ENSP00000514418.1	A0A8V8TNH6
DZANK1	ENST00000357236.8 linkuse as main transcript	c.716G>A	p.Gly239Glu	missense_variant	9/17	5		ENSP00000349774.5	A0A0A0MRE2
DZANK1	ENST00000480488.2 linkuse as main transcript	c.-92G>A		5_prime_UTR_variant	2/6	5		ENSP00000484666.1	A0A087X236
DZANK1	ENST00000377630.9 linkuse as main transcript	n.*501G>A		non_coding_transcript_exon_variant	12/20	2		ENSP00000366857.6	A0A087WTH2
DZANK1	ENST00000460891.5 linkuse as main transcript	n.*1758G>A		non_coding_transcript_exon_variant	13/14	2		ENSP00000477872.1	A0A087WTH2
DZANK1	ENST00000377630.9 linkuse as main transcript	n.*501G>A		3_prime_UTR_variant	12/20	2		ENSP00000366857.6	A0A087WTH2
DZANK1	ENST00000460891.5 linkuse as main transcript	n.*1758G>A		3_prime_UTR_variant	13/14	2		ENSP00000477872.1	A0A087WTH2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249264

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135236

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000185

AC:

AN:

1461666

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

727120

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000243

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152134

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000189

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 30, 2023

The c.1295G>A (p.G432E) alteration is located in exon 13 (coding exon 12) of the DZANK1 gene. This alteration results from a G to A substitution at nucleotide position 1295, causing the glycine (G) at amino acid position 432 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Uncertain

0.083

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.048

T;T;T;.

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.90

D;D;.;D

M_CAP

Benign

0.043

MetaRNN

Uncertain

0.55

D;D;D;D

MetaSVM

Uncertain

-0.15

MutationAssessor

Uncertain

2.7

M;.;M;.

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-3.2

D;.;.;.

REVEL

Benign

0.24

Sift

Uncertain

0.021

D;.;.;.

Sift4G

Uncertain

0.033

D;D;D;D

Polyphen

0.92

P;.;P;.

Vest4

0.61

MutPred

0.19

Gain of solvent accessibility (P = 0.0171);.;Gain of solvent accessibility (P = 0.0171);.;

MVP

0.60

MPC

0.28

ClinPred

0.98

GERP RS

5.7

Varity_R

0.32

gMVP

0.65

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over