20-18465319-A-T

Variant names:

• chr20-18465319-A-T
• rs6035051
• NM_001367614.1:c.40T>A

Variant summary

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

The NM_001367614.1(DZANK1):​c.40T>A​(p.Leu14Ile) 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. 14/21 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=0.28313893).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DZANK1	NM_001367614.1	c.40T>A	p.Leu14Ile	missense_variant	Exon 2 of 21	ENST00000699568.1	NP_001354543.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DZANK1	ENST00000699568.1	c.40T>A	p.Leu14Ile	missense_variant	Exon 2 of 21		NM_001367614.1	ENSP00000514442.1
DZANK1	ENST00000699590.1	c.40T>A	p.Leu14Ile	missense_variant	Exon 2 of 21			ENSP00000514461.1
DZANK1	ENST00000699525.1	c.40T>A	p.Leu14Ile	missense_variant	Exon 2 of 21			ENSP00000514418.1
DZANK1	ENST00000377630.9	n.40T>A		non_coding_transcript_exon_variant	Exon 2 of 20	2		ENSP00000366857.6
DZANK1	ENST00000460891.5	n.40T>A		non_coding_transcript_exon_variant	Exon 2 of 14	2		ENSP00000477872.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR 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	0.17
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0093	T;T
Eigen	Benign	0.16
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.84	T;.
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.28	T;T
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Benign	1.5	L;L
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.17
Sift	Benign	0.19	T;T
Sift4G	Benign	0.15	T;T
Polyphen		1.0	D;D
Vest4		0.13
MutPred		0.30		Loss of catalytic residue at L14 (P = 0.0029);Loss of catalytic residue at L14 (P = 0.0029);
MVP		0.47
MPC		0.30
ClinPred		0.68	D
GERP RS		2.1
Varity_R		0.077
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;