dbSNP rs1304232258: DZANK1:p.Ser727Thr (chr20-18384553-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001367614.1(DZANK1):c.2180G>C(p.Ser727Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,450,926 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S727N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DZANK1
NM_001367614.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.463

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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=0.16365919).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DZANK1	NM_001367614.1 link	c.2180G>C	p.Ser727Thr	missense_variant	Exon 21 of 21	ENST00000699568.1	NP_001354543.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DZANK1	ENST00000699568.1 link	c.2180G>C	p.Ser727Thr	missense_variant	Exon 21 of 21		NM_001367614.1	ENSP00000514442.1	A0A8V8TNE5
DZANK1	ENST00000699590.1 link	c.2138G>C	p.Ser713Thr	missense_variant	Exon 21 of 21			ENSP00000514461.1	A0A8V8TPU7
DZANK1	ENST00000699525.1 link	c.2123G>C	p.Ser708Thr	missense_variant	Exon 21 of 21			ENSP00000514418.1	A0A8V8TNH6
DZANK1	ENST00000357236.8 link	c.1526G>C	p.Ser509Thr	missense_variant	Exon 17 of 17	5		ENSP00000349774.5	A0A0A0MRE2
DZANK1	ENST00000377630.9 link	n.*1311G>C		non_coding_transcript_exon_variant	Exon 20 of 20	2		ENSP00000366857.6	A0A087WTH2
DZANK1	ENST00000377630.9 link	n.*1311G>C		3_prime_UTR_variant	Exon 20 of 20	2		ENSP00000366857.6	A0A087WTH2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1450926

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

720756

show subpopulations

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:

0.00000181

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0075

T;T;T;.

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.80

T;T;.;T

M_CAP

Benign

0.038

MetaRNN

Benign

0.16

T;T;T;T

MetaSVM

Benign

-0.56

MutationAssessor

Benign

2.0

M;.;M;.

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.7

N;.;.;.

REVEL

Benign

0.14

Sift

Benign

0.037

D;.;.;.

Sift4G

Uncertain

0.019

D;D;D;D

Polyphen

0.92

P;.;P;.

Vest4

0.15

MutPred

0.50

Gain of methylation at K706 (P = 0.1121);.;Gain of methylation at K706 (P = 0.1121);.;

MVP

0.25

MPC

0.084

ClinPred

0.61

GERP RS

1.4

Varity_R

0.071

gMVP

0.19

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over