20-18465319-A-C

Position:

• chr20-18465319-A-C

Variant summary

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

The NM_001367614.1(DZANK1):​c.40T>G​(p.Leu14Val) 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DZANK1 NM_001367614.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.69

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

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=0.3867816).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DZANK1	NM_001367614.1	c.40T>G	p.Leu14Val	missense_variant	2/21	ENST00000699568.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DZANK1	ENST00000699568.1	c.40T>G	p.Leu14Val	missense_variant	2/21		NM_001367614.1	P2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1457894 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 725034

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.0054	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	T;T
Eigen	Benign	0.17
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.63	D
LIST_S2	Uncertain	0.91	D;.
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.39	T;T
MetaSVM	Benign	-0.30	T
MutationAssessor	Uncertain	2.4	M;M
MutationTaster	Benign	0.69	P;P;P;P
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.18
Sift	Uncertain	0.0090	D;D
Sift4G	Uncertain	0.044	D;D
Polyphen		1.0	D;D
Vest4		0.40
MutPred		0.29		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP		0.52
MPC		0.29
ClinPred		0.89	D
GERP RS		2.1
Varity_R		0.12
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs6035051; hg19: chr20-18445963;