Variant 16-4698042-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_133450.4(ANKS3):c.1745C>T(p.Ser582Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00148 in 1,609,660 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00091 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0015 ( 5 hom. )

Consequence

ANKS3
NM_133450.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.68

Variant links:

Genes affected

ANKS3 (HGNC:29422): (ankyrin repeat and sterile alpha motif domain containing 3) Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ANKS3 links:

ANKS3 (HGNC:):

ANKS3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007784158).

BP6

Variant 16-4698042-G-A is Benign according to our data. Variant chr16-4698042-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3033093.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKS3	NM_133450.4 linkuse as main transcript	c.1745C>T	p.Ser582Leu	missense_variant	15/18	ENST00000304283.9	NP_597707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKS3	ENST00000304283.9 linkuse as main transcript	c.1745C>T	p.Ser582Leu	missense_variant	15/18	2	NM_133450.4	ENSP00000304586.4		Q6ZW76-1

Frequencies

GnomAD3 genomes

AF:

0.000913

AC:

139

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00156

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000865

AC:

208

AN:

240406

Hom.:

AF XY:

0.000895

AC XY:

117

AN XY:

130786

show subpopulations

Gnomad AFR exome

AF:

0.000268

Gnomad AMR exome

AF:

0.000237

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000135

Gnomad FIN exome

AF:

0.000392

Gnomad NFE exome

AF:

0.00166

Gnomad OTH exome

AF:

0.000684

GnomAD4 exome

AF:

0.00154

AC:

2247

AN:

1457346

Hom.:

Cov.:

AF XY:

0.00149

AC XY:

1082

AN XY:

724606

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.000158

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000117

Gnomad4 FIN exome

AF:

0.000327

Gnomad4 NFE exome

AF:

0.00193

Gnomad4 OTH exome

AF:

0.000947

GnomAD4 genome

AF:

0.000906

AC:

138

AN:

152314

Hom.:

Cov.:

AF XY:

0.000752

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00154

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00154

Hom.:

Bravo

AF:

0.00109

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00174

AC:

ExAC

AF:

0.000685

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ANKS3-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 15, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0031

T;T;T;T;.

Eigen

Benign

0.12

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.89

D;D;D;.;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.0078

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

L;.;.;L;.

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.5

.;.;N;N;.

REVEL

Benign

0.11

Sift

Benign

0.73

.;.;T;T;.

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.95

P;.;.;P;.

Vest4

0.46

MVP

0.52

MPC

0.054

ClinPred

0.029

GERP RS

4.5

Varity_R

0.084

gMVP

0.14

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over