9-98770938-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_173551.5(ANKS6):c.1930G>A(p.Val644Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.952 in 1,586,358 control chromosomes in the GnomAD database, including 720,902 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.94 ( 68030 hom., cov: 34)

Exomes 𝑓: 0.95 ( 652872 hom. )

Consequence

ANKS6
NM_173551.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.31

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.176339E-7).

BP6

Variant 9-98770938-C-T is Benign according to our data. Variant chr9-98770938-C-T is described in ClinVar as [Benign]. Clinvar id is 262847.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKS6	NM_173551.5 link	c.1930G>A	p.Val644Ile	missense_variant	Exon 10 of 15	ENST00000353234.5	NP_775822.3	Q68DC2-1B3KXP1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ANKS6	ENST00000353234.5 link	c.1930G>A	p.Val644Ile	missense_variant	Exon 10 of 15	1	NM_173551.5	ENSP00000297837.6	Q68DC2-1
ANKS6	ENST00000375019.6 link	c.1027G>A	p.Val343Ile	missense_variant	Exon 9 of 15	5		ENSP00000364159.2	A0A0A0MRS7
ANKS6	ENST00000444472.5 link	c.334G>A	p.Val112Ile	missense_variant	Exon 3 of 9	2		ENSP00000398648.1	H7C163
ANKS6	ENST00000634393.1 link	n.1030G>A		non_coding_transcript_exon_variant	Exon 8 of 15	5

Frequencies

GnomAD3 genomes

AF:

0.944

AC:

143596

AN:

152180

Hom.:

67989

Cov.:

show subpopulations

Gnomad AFR

AF:

0.953

Gnomad AMI

AF:

0.999

Gnomad AMR

AF:

0.882

Gnomad ASJ

AF:

0.948

Gnomad EAS

AF:

0.719

Gnomad SAS

AF:

0.868

Gnomad FIN

AF:

0.990

Gnomad MID

AF:

0.946

Gnomad NFE

AF:

0.966

Gnomad OTH

AF:

0.942

GnomAD3 exomes

AF:

0.919

AC:

211326

AN:

229872

Hom.:

98015

AF XY:

0.924

AC XY:

115255

AN XY:

124798

show subpopulations

Gnomad AFR exome

AF:

0.953

Gnomad AMR exome

AF:

0.800

Gnomad ASJ exome

AF:

0.951

Gnomad EAS exome

AF:

0.718

Gnomad SAS exome

AF:

0.888

Gnomad FIN exome

AF:

0.992

Gnomad NFE exome

AF:

0.968

Gnomad OTH exome

AF:

0.943

GnomAD4 exome

AF:

0.953

AC:

1366317

AN:

1434060

Hom.:

652872

Cov.:

AF XY:

0.952

AC XY:

677690

AN XY:

712228

show subpopulations

Gnomad4 AFR exome

AF:

0.956

Gnomad4 AMR exome

AF:

0.813

Gnomad4 ASJ exome

AF:

0.948

Gnomad4 EAS exome

AF:

0.733

Gnomad4 SAS exome

AF:

0.885

Gnomad4 FIN exome

AF:

0.992

Gnomad4 NFE exome

AF:

0.969

Gnomad4 OTH exome

AF:

0.947

GnomAD4 genome

AF:

0.943

AC:

143690

AN:

152298

Hom.:

68030

Cov.:

AF XY:

0.941

AC XY:

70062

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.953

Gnomad4 AMR

AF:

0.881

Gnomad4 ASJ

AF:

0.948

Gnomad4 EAS

AF:

0.719

Gnomad4 SAS

AF:

0.868

Gnomad4 FIN

AF:

0.990

Gnomad4 NFE

AF:

0.966

Gnomad4 OTH

AF:

0.940

Alfa

AF:

0.954

Hom.:

164064

Bravo

AF:

0.934

TwinsUK

AF:

0.965

AC:

3577

ALSPAC

AF:

0.964

AC:

3717

ESP6500AA

AF:

0.955

AC:

3644

ESP6500EA

AF:

0.967

AC:

7978

ExAC

AF:

0.921

AC:

111266

Asia WGS

AF:

0.828

AC:

2878

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Nephronophthisis 16

Benign:2

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

0.079

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.48

CADD

Benign

2.4

DANN

Benign

0.82

DEOGEN2

Benign

0.0075

.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.053

LIST_S2

Benign

0.47

T;T

MetaRNN

Benign

6.2e-7

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.035

.;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.020

N;N

REVEL

Benign

0.070

Sift

Benign

1.0

T;T

Sift4G

Benign

0.36

T;T

Polyphen

0.0

.;B

Vest4

0.031

MPC

0.082

ClinPred

0.00073

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.017

gMVP

0.11

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