20-18414380-G-C

Position:

chr20-18414380-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001367614.1(DZANK1):c.1267C>G(p.Leu423Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000173 in 1,613,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. 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: -0.717

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06818259).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DZANK1	NM_001367614.1 linkuse as main transcript	c.1267C>G	p.Leu423Val	missense_variant	12/21	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.1267C>G	p.Leu423Val	missense_variant	12/21		NM_001367614.1	ENSP00000514442.1	A0A8V8TNE5
DZANK1	ENST00000699590.1 linkuse as main transcript	c.1225C>G	p.Leu409Val	missense_variant	12/21			ENSP00000514461.1	A0A8V8TPU7
DZANK1	ENST00000699525.1 linkuse as main transcript	c.1210C>G	p.Leu404Val	missense_variant	12/21			ENSP00000514418.1	A0A8V8TNH6
DZANK1	ENST00000357236.8 linkuse as main transcript	c.613C>G	p.Leu205Val	missense_variant	8/17	5		ENSP00000349774.5	A0A0A0MRE2
DZANK1	ENST00000377630.9 linkuse as main transcript	n.*398C>G		non_coding_transcript_exon_variant	11/20	2		ENSP00000366857.6	A0A087WTH2
DZANK1	ENST00000460891.5 linkuse as main transcript	n.*1655C>G		non_coding_transcript_exon_variant	12/14	2		ENSP00000477872.1	A0A087WTH2
DZANK1	ENST00000377630.9 linkuse as main transcript	n.*398C>G		3_prime_UTR_variant	11/20	2		ENSP00000366857.6	A0A087WTH2
DZANK1	ENST00000460891.5 linkuse as main transcript	n.*1655C>G		3_prime_UTR_variant	12/14	2		ENSP00000477872.1	A0A087WTH2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152158

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:

0.0000241

AC:

AN:

249180

Hom.:

AF XY:

0.0000370

AC XY:

AN XY:

135182

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:

0.0000531

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000185

AC:

AN:

1461686

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727126

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:

152158

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74342

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:

0.0000847

Hom.:

Bravo

AF:

0.0000264

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000248

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

Jan 17, 2024

The c.1210C>G (p.L404V) alteration is located in exon 12 (coding exon 11) of the DZANK1 gene. This alteration results from a C to G substitution at nucleotide position 1210, causing the leucine (L) at amino acid position 404 to be replaced by a valine (V). 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

Benign

0.067

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.38

CADD

Benign

0.64

DANN

Benign

0.87

DEOGEN2

Benign

0.0017

T;T;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.55

T;T;.;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.068

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.94

L;.;L;.

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.31

N;.;.;.

REVEL

Benign

0.20

Sift

Benign

0.45

T;.;.;.

Sift4G

Benign

0.54

T;T;T;T

Polyphen

0.016

B;.;B;.

Vest4

0.030

MutPred

0.14

Gain of helix (P = 0.0496);.;Gain of helix (P = 0.0496);.;

MVP

0.16

MPC

0.042

ClinPred

0.033

GERP RS

-2.4

Varity_R

0.035

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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