20-18384410-C-G

Variant names:

• chr20-18384410-C-G
• NM_001367614.1:c.2323G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001367614.1(DZANK1):​c.2323G>C​(p.Asp775His) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: DZANK1 NM_001367614.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.19
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20000839).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DZANK1	NM_001367614.1	MANE Select	c.2323G>C	p.Asp775His	missense	Exon 21 of 21	NP_001354543.1	A0A8V8TNE5
	DZANK1	NM_001367617.1		c.2323G>C	p.Asp775His	missense	Exon 21 of 21	NP_001354546.1	A0A8V8TNE5
	DZANK1	NM_001367618.1		c.2323G>C	p.Asp775His	missense	Exon 21 of 21	NP_001354547.1	A0A8V8TNE5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DZANK1	ENST00000699568.1	MANE Select	c.2323G>C	p.Asp775His	missense	Exon 21 of 21	ENSP00000514442.1	A0A8V8TNE5
	DZANK1	ENST00000699590.1		c.2281G>C	p.Asp761His	missense	Exon 21 of 21	ENSP00000514461.1	A0A8V8TPU7
	DZANK1	ENST00000699525.1		c.2266G>C	p.Asp756His	missense	Exon 21 of 21	ENSP00000514418.1	A0A8V8TNH6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0034	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.2
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.11
Sift	Uncertain	0.015	D
Sift4G	Benign	0.11	T
Polyphen		0.84	P
Vest4		0.18
MutPred		0.44		Loss of stability (P = 0.0731)
MVP		0.45
MPC		0.18
ClinPred		0.81	D
GERP RS		3.5
Varity_R		0.077
gMVP		0.46
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

hg19: chr20-18365054;