rs41283630

Positions:

Variant summary

Our verdict is Benign. Variant got -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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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

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=0.005607575).

BP6

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

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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKS6	NM_173551.5 linkuse as main transcript	c.664C>T	p.Arg222Trp	missense_variant	2/15	ENST00000353234.5	NP_775822.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKS6	ENST00000353234.5 linkuse as main transcript	c.664C>T	p.Arg222Trp	missense_variant	2/15	1	NM_173551.5	ENSP00000297837	P1	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

GnomAD3 exomes

AF:

0.00806

AC:

1967

AN:

244172

Hom.:

AF XY:

0.00895

AC XY:

1190

AN XY:

132982

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 SAS exome

AF:

0.0206

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

Gnomad4 AFR exome

AF:

0.00132

Gnomad4 AMR exome

AF:

0.00471

Gnomad4 ASJ exome

AF:

0.0150

Gnomad4 EAS exome

AF:

0.00985

Gnomad4 SAS exome

AF:

0.0211

Gnomad4 FIN exome

AF:

0.000448

Gnomad4 NFE exome

AF:

0.00610

Gnomad4 OTH exome

AF:

0.00848

GnomAD4 genome

AF:

0.00523

AC:

797

AN:

152306

Hom.:

Cov.:

AF XY:

0.00506

AC XY:

377

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00147

Gnomad4 AMR

AF:

0.00458

Gnomad4 ASJ

AF:

0.0132

Gnomad4 EAS

AF:

0.0174

Gnomad4 SAS

AF:

0.0236

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00585

Gnomad4 OTH

AF:

0.00757

Alfa

AF:

0.00637

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

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 19, 2021	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Nephronophthisis 16

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 18, 2024

- -

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

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

MutationTaster

Benign

0.72

D;D;D;N

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

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