Variant rs76903503 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_173551.5(ANKS6):c.330C>T(p.Tyr110=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 1,412,228 control chromosomes in the GnomAD database, including 10,695 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1097 hom., cov: 33)

Exomes 𝑓: 0.12 ( 9598 hom. )

Consequence

ANKS6
NM_173551.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.94

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 9-98796162-G-A is Benign according to our data. Variant chr9-98796162-G-A is described in ClinVar as [Benign]. Clinvar id is 262851.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.94 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKS6	NM_173551.5 linkuse as main transcript	c.330C>T	p.Tyr110=	synonymous_variant	1/15	ENST00000353234.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKS6	ENST00000353234.5 linkuse as main transcript	c.330C>T	p.Tyr110=	synonymous_variant	1/15	1	NM_173551.5	P1	Q68DC2-1
ANKS6	ENST00000375019.6 linkuse as main transcript	c.-42+522C>T		intron_variant		5
ANKS6	ENST00000471846.1 linkuse as main transcript	n.378C>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

16112

AN:

151990

Hom.:

1095

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0374

Gnomad AMI

AF:

0.126

Gnomad AMR

AF:

0.155

Gnomad ASJ

AF:

0.0905

Gnomad EAS

AF:

0.216

Gnomad SAS

AF:

0.147

Gnomad FIN

AF:

0.190

Gnomad MID

AF:

0.105

Gnomad NFE

AF:

0.113

Gnomad OTH

AF:

0.114

GnomAD3 exomes

AF:

0.141

AC:

7877

AN:

55872

Hom.:

652

AF XY:

0.137

AC XY:

4479

AN XY:

32698

show subpopulations

Gnomad AFR exome

AF:

0.0478

Gnomad AMR exome

AF:

0.205

Gnomad ASJ exome

AF:

0.0848

Gnomad EAS exome

AF:

0.208

Gnomad SAS exome

AF:

0.146

Gnomad FIN exome

AF:

0.190

Gnomad NFE exome

AF:

0.112

Gnomad OTH exome

AF:

0.123

GnomAD4 exome

AF:

0.119

AC:

149385

AN:

1260130

Hom.:

9598

Cov.:

AF XY:

0.119

AC XY:

73681

AN XY:

618334

show subpopulations

Gnomad4 AFR exome

AF:

0.0313

Gnomad4 AMR exome

AF:

0.191

Gnomad4 ASJ exome

AF:

0.0817

Gnomad4 EAS exome

AF:

0.226

Gnomad4 SAS exome

AF:

0.144

Gnomad4 FIN exome

AF:

0.185

Gnomad4 NFE exome

AF:

0.113

Gnomad4 OTH exome

AF:

0.123

GnomAD4 genome

AF:

0.106

AC:

16118

AN:

152098

Hom.:

1097

Cov.:

AF XY:

0.111

AC XY:

8259

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.0374

Gnomad4 AMR

AF:

0.155

Gnomad4 ASJ

AF:

0.0905

Gnomad4 EAS

AF:

0.216

Gnomad4 SAS

AF:

0.147

Gnomad4 FIN

AF:

0.190

Gnomad4 NFE

AF:

0.113

Gnomad4 OTH

AF:

0.112

Alfa

AF:

0.107

Hom.:

147

Bravo

AF:

0.104

Asia WGS

AF:

0.194

AC:

670

AN:

3464

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Nephronophthisis 16

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

ANKS6-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 26, 2022

This variant is classified as 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

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.97

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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