20-18384491-C-T

Variant names:

• chr20-18384491-C-T
• rs752231081
• NM_001367614.1:c.2242G>A

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.2242G>A​(p.Asp748Asn) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D748Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: DZANK1 NM_001367614.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65
• Publications: 1 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=0.13427204).

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.2242G>A	p.Asp748Asn	missense	Exon 21 of 21	NP_001354543.1	A0A8V8TNE5
	DZANK1	NM_001367617.1		c.2242G>A	p.Asp748Asn	missense	Exon 21 of 21	NP_001354546.1	A0A8V8TNE5
	DZANK1	NM_001367618.1		c.2242G>A	p.Asp748Asn	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.2242G>A	p.Asp748Asn	missense	Exon 21 of 21	ENSP00000514442.1	A0A8V8TNE5
	DZANK1	ENST00000699590.1		c.2200G>A	p.Asp734Asn	missense	Exon 21 of 21	ENSP00000514461.1	A0A8V8TPU7
	DZANK1	ENST00000699525.1		c.2185G>A	p.Asp729Asn	missense	Exon 21 of 21	ENSP00000514418.1	A0A8V8TNH6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000407 AC: 1 AN: 245558 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000896

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000827 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0041	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.6
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.068
Sift	Benign	0.51	T
Sift4G	Benign	0.30	T
Polyphen		0.036	B
Vest4		0.053
MutPred		0.53		Loss of phosphorylation at T720 (P = 0.1428)
MVP		0.25
MPC		0.041
ClinPred		0.14	T
GERP RS		3.5
Varity_R		0.058
gMVP		0.13
Mutation Taster		=95/5	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: rs752231081; hg19: chr20-18365135;