20-18414416-A-T

Position:

• chr20-18414416-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001367614.1(DZANK1):​c.1231T>A​(p.Ser411Thr) 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. 16/21 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: 32)
• Consequence: DZANK1 NM_001367614.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.841

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]

DZANK1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08436793).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DZANK1	NM_001367614.1	c.1231T>A	p.Ser411Thr	missense_variant	12/21	ENST00000699568.1	NP_001354543.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DZANK1	ENST00000699568.1	c.1231T>A	p.Ser411Thr	missense_variant	12/21		NM_001367614.1	ENSP00000514442.1
DZANK1	ENST00000699590.1	c.1189T>A	p.Ser397Thr	missense_variant	12/21			ENSP00000514461.1
DZANK1	ENST00000699525.1	c.1174T>A	p.Ser392Thr	missense_variant	12/21			ENSP00000514418.1
DZANK1	ENST00000357236.8	c.577T>A	p.Ser193Thr	missense_variant	8/17	5		ENSP00000349774.5
DZANK1	ENST00000377630.9	n.*362T>A		non_coding_transcript_exon_variant	11/20	2		ENSP00000366857.6
DZANK1	ENST00000460891.5	n.*1619T>A		non_coding_transcript_exon_variant	12/14	2		ENSP00000477872.1
DZANK1	ENST00000377630.9	n.*362T>A		3_prime_UTR_variant	11/20	2		ENSP00000366857.6
DZANK1	ENST00000460891.5	n.*1619T>A		3_prime_UTR_variant	12/14	2		ENSP00000477872.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 03, 2024

The c.1174T>A (p.S392T) alteration is located in exon 12 (coding exon 11) of the DZANK1 gene. This alteration results from a T to A substitution at nucleotide position 1174, causing the serine (S) at amino acid position 392 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	16
DANN	Benign	0.68
DEOGEN2	Benign	0.0014	T;T;T;.
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.52
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.56	T;T;.;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.084	T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.5	L;.;L;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.76	N;.;.;.
REVEL	Benign	0.022
Sift	Benign	0.31	T;.;.;.
Sift4G	Benign	0.40	T;T;T;T
Polyphen		0.0020	B;.;B;.
Vest4		0.11
MutPred		0.36		Loss of helix (P = 0.0017);.;Loss of helix (P = 0.0017);.;
MVP		0.25
MPC		0.039
ClinPred		0.10	T
GERP RS		1.8
Varity_R		0.053
gMVP		0.34

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-18395060;