rs148071928

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_173551.5(ANKS6):c.1565A>G(p.Asn522Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00258 in 1,614,068 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 18/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 6 hom. )

Consequence

ANKS6
NM_173551.5 missense, splice_region

Scores

Splicing: ADA: 0.0004231

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.332

Publications

7 publications found

Variant links:

Genes affected

ANKS6 (HGNC:26724): (ankyrin repeat and sterile alpha motif domain containing 6) This gene encodes a protein containing multiple ankyrin repeats and a SAM domain. It is thought that this protein may localize to the proximal region of the primary cilium, and may play a role in renal and cardiovascular development. Mutations in this gene have been shown to cause a form of nephronophthisis (NPHP16), a chronic tubulo-interstitial nephritis. [provided by RefSeq, Jul 2015]

ANKS6 Gene-Disease associations (from GenCC):

nephronophthisis 16
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
nephronophthisis 1
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
nephronophthisis 2
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ANKS6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037843883).

BP6

Variant 9-98778228-T-C is Benign according to our data. Variant chr9-98778228-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 541404.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKS6	NM_173551.5 link	c.1565A>G	p.Asn522Ser	missense_variant, splice_region_variant	Exon 7 of 15	ENST00000353234.5	NP_775822.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
ANKS6	ENST00000353234.5 link	c.1565A>G	p.Asn522Ser	missense_variant, splice_region_variant	Exon 7 of 15	1	NM_173551.5	ENSP00000297837.6
ANKS6	ENST00000375019.6 link	c.662A>G	p.Asn221Ser	missense_variant, splice_region_variant	Exon 6 of 15	5		ENSP00000364159.2
ANKS6	ENST00000634393.1 link	n.665A>G		splice_region_variant, non_coding_transcript_exon_variant	Exon 5 of 15	5

Frequencies

GnomAD3 genomes

AF:

0.00225

AC:

342

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00499

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00375

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00262

AC:

652

AN:

249252

AF XY:

0.00276

show subpopulations

Gnomad AFR exome

AF:

0.000388

Gnomad AMR exome

AF:

0.000870

Gnomad ASJ exome

AF:

0.000696

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00478

Gnomad NFE exome

AF:

0.00429

Gnomad OTH exome

AF:

0.00281

GnomAD4 exome

AF:

0.00261

AC:

3816

AN:

1461808

Hom.:

Cov.:

AF XY:

0.00257

AC XY:

1870

AN XY:

727194

show subpopulations

African (AFR)

AF:

0.000388

AC:

AN:

33476

American (AMR)

AF:

0.000939

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.000383

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.000232

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00511

AC:

273

AN:

53418

Middle Eastern (MID)

AF:

0.00156

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00298

AC:

3313

AN:

1111958

Other (OTH)

AF:

0.00225

AC:

136

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

216

432

649

865

1081

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

192

288

384

480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00225

AC:

342

AN:

152260

Hom.:

Cov.:

AF XY:

0.00227

AC XY:

169

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.000385

AC:

AN:

41550

American (AMR)

AF:

0.000588

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000208

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00499

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00375

AC:

255

AN:

68014

Other (OTH)

AF:

0.00237

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00306

Hom.:

Bravo

AF:

0.00185

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.00102

AC:

ESP6500EA

AF:

0.00337

AC:

ExAC

AF:

0.00324

AC:

392

EpiCase

AF:

0.00463

EpiControl

AF:

0.00373

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Nephronophthisis 16

Benign:1

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Oct 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ANKS6: BP4 -

ANKS6-related disorder

Benign:1

Sep 08, 2020

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

0.053

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.66

CADD

Benign

2.7

(source)

DANN

Benign

0.24

DEOGEN2

Benign

0.0056

.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.69

T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.0038

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.41

.;N

PhyloP100

-0.33

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.28

N;N

REVEL

Benign

0.029

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0030

.;B

Vest4

0.15

MVP

0.29

MPC

0.080

ClinPred

0.00081

GERP RS

-1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.022

gMVP

0.060

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00042

dbscSNV1_RF

Benign

0.19

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over