9-98790308-C-T

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.658G>A(p.Ala220Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00146 in 1,607,358 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A220P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0027 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 10 hom. )

Consequence

ANKS6
NM_173551.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.00900

Publications

8 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=0.003323108).

BP6

Variant 9-98790308-C-T is Benign according to our data. Variant chr9-98790308-C-T is described in ClinVar as Benign. ClinVar VariationId is 474454.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKS6	NM_173551.5 link	c.658G>A	p.Ala220Thr	missense_variant	Exon 2 of 15	ENST00000353234.5	NP_775822.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKS6	ENST00000353234.5 link	c.658G>A	p.Ala220Thr	missense_variant	Exon 2 of 15	1	NM_173551.5	ENSP00000297837.6

Frequencies

GnomAD3 genomes

AF:

0.00269

AC:

409

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00528

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00366

Gnomad ASJ

AF:

0.0184

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000867

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00197

AC:

481

AN:

244436

AF XY:

0.00189

show subpopulations

Gnomad AFR exome

AF:

0.00493

Gnomad AMR exome

AF:

0.00276

Gnomad ASJ exome

AF:

0.0165

Gnomad EAS exome

AF:

0.000112

Gnomad FIN exome

AF:

0.0000496

Gnomad NFE exome

AF:

0.00106

Gnomad OTH exome

AF:

0.00417

GnomAD4 exome

AF:

0.00134

AC:

1944

AN:

1455020

Hom.:

Cov.:

AF XY:

0.00130

AC XY:

940

AN XY:

722866

show subpopulations

African (AFR)

AF:

0.00647

AC:

216

AN:

33388

American (AMR)

AF:

0.00282

AC:

126

AN:

44624

Ashkenazi Jewish (ASJ)

AF:

0.0152

AC:

397

AN:

26070

East Asian (EAS)

AF:

0.0000759

AC:

AN:

39506

South Asian (SAS)

AF:

0.0000813

AC:

AN:

86140

European-Finnish (FIN)

AF:

0.0000389

AC:

AN:

51408

Middle Eastern (MID)

AF:

0.00556

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.000864

AC:

957

AN:

1108052

Other (OTH)

AF:

0.00340

AC:

204

AN:

60076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

134

268

403

537

671

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

150

200

250

<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:

0.00269

AC:

410

AN:

152338

Hom.:

Cov.:

AF XY:

0.00274

AC XY:

204

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.00529

AC:

220

AN:

41578

American (AMR)

AF:

0.00366

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0184

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000867

AC:

AN:

68030

Other (OTH)

AF:

0.00331

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

102

128

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:

0.00202

Hom.:

Bravo

AF:

0.00323

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00368

AC:

ESP6500EA

AF:

0.00120

AC:

ExAC

AF:

0.00159

AC:

192

EpiCase

AF:

0.00185

EpiControl

AF:

0.00190

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Oct 02, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nephronophthisis 16

Benign:1

Jan 22, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.21

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.0069

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.41

M_CAP

Benign

0.023

MetaRNN

Benign

0.0033

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

0.0090

PrimateAI

Benign

0.23

PROVEAN

Benign

0.47

REVEL

Benign

0.014

Sift

Benign

0.71

Sift4G

Benign

0.87

Polyphen

0.0010

Vest4

0.11

MVP

0.28

MPC

0.098

ClinPred

0.00053

GERP RS

-1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.026

gMVP

0.21

Mutation Taster

=99/1

polymorphism

(source)

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

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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