rs41283630

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_173551.5(ANKS6):c.664C>T(p.Arg222Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00686 in 1,606,732 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R222Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0052 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0070 ( 62 hom. )

Consequence

ANKS6
NM_173551.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.54

Publications

11 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005607575).

BP6

Variant 9-98790302-G-A is Benign according to our data. Variant chr9-98790302-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262856.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00523 (797/152306) while in subpopulation SAS AF = 0.0236 (114/4822). AF 95% confidence interval is 0.0201. There are 6 homozygotes in GnomAd4. There are 377 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKS6	NM_173551.5 link	c.664C>T	p.Arg222Trp	missense_variant	Exon 2 of 15	ENST00000353234.5	NP_775822.3	Q68DC2-1B3KXP1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKS6	ENST00000353234.5 link	c.664C>T	p.Arg222Trp	missense_variant	Exon 2 of 15	1	NM_173551.5	ENSP00000297837.6		Q68DC2-1

Frequencies

GnomAD3 genomes

AF:

0.00523

AC:

796

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00147

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00458

Gnomad ASJ

AF:

0.0132

Gnomad EAS

AF:

0.0173

Gnomad SAS

AF:

0.0234

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00585

Gnomad OTH

AF:

0.00765

GnomAD2 exomes

AF:

0.00806

AC:

1967

AN:

244172

AF XY:

0.00895

show subpopulations

Gnomad AFR exome

AF:

0.000855

Gnomad AMR exome

AF:

0.00517

Gnomad ASJ exome

AF:

0.0130

Gnomad EAS exome

AF:

0.0176

Gnomad FIN exome

AF:

0.000500

Gnomad NFE exome

AF:

0.00579

Gnomad OTH exome

AF:

0.00952

GnomAD4 exome

AF:

0.00703

AC:

10227

AN:

1454426

Hom.:

Cov.:

AF XY:

0.00741

AC XY:

5353

AN XY:

722448

show subpopulations

African (AFR)

AF:

0.00132

AC:

AN:

33378

American (AMR)

AF:

0.00471

AC:

210

AN:

44608

Ashkenazi Jewish (ASJ)

AF:

0.0150

AC:

390

AN:

26062

East Asian (EAS)

AF:

0.00985

AC:

389

AN:

39488

South Asian (SAS)

AF:

0.0211

AC:

1821

AN:

86126

European-Finnish (FIN)

AF:

0.000448

AC:

AN:

51324

Middle Eastern (MID)

AF:

0.0148

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00610

AC:

6756

AN:

1107652

Other (OTH)

AF:

0.00848

AC:

509

AN:

60036

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

720

1441

2161

2882

3602

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

292

584

876

1168

1460

<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:

0.00523

AC:

797

AN:

152306

Hom.:

Cov.:

AF XY:

0.00506

AC XY:

377

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.00147

AC:

AN:

41576

American (AMR)

AF:

0.00458

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0132

AC:

AN:

3472

East Asian (EAS)

AF:

0.0174

AC:

AN:

5176

South Asian (SAS)

AF:

0.0236

AC:

114

AN:

4822

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00585

AC:

398

AN:

68018

Other (OTH)

AF:

0.00757

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

119

159

199

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00634

Hom.:

Bravo

AF:

0.00486

TwinsUK

AF:

0.00701

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.00148

AC:

ESP6500EA

AF:

0.00744

AC:

ExAC

AF:

0.00764

AC:

922

Asia WGS

AF:

0.0210

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 19, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nephronophthisis 16

Benign:1

Jan 26, 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

0.084

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.78

MetaRNN

Benign

0.0056

MetaSVM

Benign

-0.69

MutationAssessor

Benign

1.5

PhyloP100

2.5

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.12

Sift

Benign

0.034

Sift4G

Uncertain

0.0040

Polyphen

0.081

Vest4

0.24

MVP

0.64

MPC

0.11

ClinPred

0.022

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.063

gMVP

0.60

Mutation Taster

=97/3

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