chr20-18433712-A-C

Variant names:

• chr20-18433712-A-C
• rs6035042
• NM_001367614.1:c.858T>G

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001367614.1(DZANK1):​c.858T>G​(p.Cys286Trp) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: DZANK1 NM_001367614.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.821
• Publications: 25 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]

RNA5SP476 (HGNC:43376): (RNA, 5S ribosomal pseudogene 476)

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.981

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DZANK1	NM_001367614.1	MANE Select	c.858T>G	p.Cys286Trp	missense	Exon 9 of 21	NP_001354543.1
	DZANK1	NM_001367617.1		c.858T>G	p.Cys286Trp	missense	Exon 9 of 21	NP_001354546.1
	DZANK1	NM_001367618.1		c.858T>G	p.Cys286Trp	missense	Exon 9 of 21	NP_001354547.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DZANK1	ENST00000699568.1	MANE Select	c.858T>G	p.Cys286Trp	missense	Exon 9 of 21	ENSP00000514442.1
	DZANK1	ENST00000699590.1		c.816T>G	p.Cys272Trp	missense	Exon 9 of 21	ENSP00000514461.1
	DZANK1	ENST00000699525.1		c.801T>G	p.Cys267Trp	missense	Exon 9 of 21	ENSP00000514418.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 60

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.089	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.40	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Benign	-0.64	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		0.82
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-8.8	D
REVEL	Uncertain	0.48
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.90
MutPred		0.75		Loss of sheet (P = 0.007)
MVP		0.29
MPC		0.33
ClinPred		1.0	D
GERP RS		0.12
PromoterAI		-0.00060	Neutral
Varity_R		0.92
gMVP		0.85
Mutation Taster		=64/36	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

dbSNP: rs6035042; hg19: chr20-18414356;