20-18389770-A-C

Variant names:

• chr20-18389770-A-C
• rs767640361
• NM_001367614.1:c.2024T>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001367614.1(DZANK1):​c.2024T>G​(p.Met675Arg) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DZANK1 NM_001367614.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.00

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]

LOC124904877 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2948225).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DZANK1	NM_001367614.1	c.2024T>G	p.Met675Arg	missense_variant	Exon 19 of 21	ENST00000699568.1	NP_001354543.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DZANK1	ENST00000699568.1	c.2024T>G	p.Met675Arg	missense_variant	Exon 19 of 21		NM_001367614.1	ENSP00000514442.1
DZANK1	ENST00000699590.1	c.1982T>G	p.Met661Arg	missense_variant	Exon 19 of 21			ENSP00000514461.1
DZANK1	ENST00000699525.1	c.1967T>G	p.Met656Arg	missense_variant	Exon 19 of 21			ENSP00000514418.1
DZANK1	ENST00000357236.8	c.1370T>G	p.Met457Arg	missense_variant	Exon 15 of 17	5		ENSP00000349774.5
DZANK1	ENST00000377630.9	n.*1155T>G		non_coding_transcript_exon_variant	Exon 18 of 20	2		ENSP00000366857.6
DZANK1	ENST00000377630.9	n.*1155T>G		3_prime_UTR_variant	Exon 18 of 20	2		ENSP00000366857.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 24, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1949T>G (p.M650R) alteration is located in exon 19 (coding exon 18) of the DZANK1 gene. This alteration results from a T to G substitution at nucleotide position 1949, causing the methionine (M) at amino acid position 650 to be replaced by an arginine (R). 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	0.10
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.040	T;T;T;.
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.48	T;T;.;T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.29	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.46	N;.;N;.
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.5	D;.;.;.
REVEL	Benign	0.22
Sift	Benign	0.055	T;.;.;.
Sift4G	Uncertain	0.010	D;D;D;D
Polyphen		0.83	P;.;P;.
Vest4		0.35
MutPred		0.41		Gain of solvent accessibility (P = 0.0171);.;Gain of solvent accessibility (P = 0.0171);.;
MVP		0.44
MPC		0.054
ClinPred		0.47	T
GERP RS		4.8
Varity_R		0.43
gMVP		0.52

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

Other links and lift over

dbSNP: rs767640361; hg19: chr20-18370414;