Variant rs138948716 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.165C>T(p.Ala55Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 1,209,356 control chromosomes in the GnomAD database, including 66,736 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6599 hom., cov: 33)

Exomes 𝑓: 0.33 ( 60137 hom. )

Consequence

ANKS6
NM_173551.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.419

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:

ANKS6 (HGNC:):

ANKS6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 9-98796327-G-A is Benign according to our data. Variant chr9-98796327-G-A is described in ClinVar as [Benign]. Clinvar id is 262843.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.419 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKS6	NM_173551.5 linkuse as main transcript	c.165C>T	p.Ala55Ala	synonymous_variant	1/15	ENST00000353234.5	NP_775822.3	Q68DC2-1B3KXP1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ANKS6	ENST00000353234.5 linkuse as main transcript	c.165C>T	p.Ala55Ala	synonymous_variant	1/15	1	NM_173551.5	ENSP00000297837.6	Q68DC2-1
ANKS6	ENST00000375019.6 linkuse as main transcript	c.-42+357C>T		intron_variant		5		ENSP00000364159.2	A0A0A0MRS7
ANKS6	ENST00000471846.1 linkuse as main transcript	n.213C>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.283

AC:

42190

AN:

149218

Hom.:

6594

Cov.:

show subpopulations

Gnomad AFR

AF:

0.137

Gnomad AMI

AF:

0.344

Gnomad AMR

AF:

0.288

Gnomad ASJ

AF:

0.296

Gnomad EAS

AF:

0.358

Gnomad SAS

AF:

0.351

Gnomad FIN

AF:

0.401

Gnomad MID

AF:

0.312

Gnomad NFE

AF:

0.341

Gnomad OTH

AF:

0.287

GnomAD3 exomes

AF:

0.438

AC:

402

AN:

918

Hom.:

AF XY:

0.438

AC XY:

248

AN XY:

566

show subpopulations

Gnomad AFR exome

AF:

0.375

Gnomad AMR exome

AF:

0.471

Gnomad ASJ exome

AF:

0.391

Gnomad EAS exome

AF:

0.500

Gnomad SAS exome

AF:

0.554

Gnomad FIN exome

AF:

0.574

Gnomad NFE exome

AF:

0.402

Gnomad OTH exome

AF:

0.433

GnomAD4 exome

AF:

0.333

AC:

353431

AN:

1060030

Hom.:

60137

Cov.:

AF XY:

0.335

AC XY:

168219

AN XY:

502518

show subpopulations

Gnomad4 AFR exome

AF:

0.125

Gnomad4 AMR exome

AF:

0.316

Gnomad4 ASJ exome

AF:

0.291

Gnomad4 EAS exome

AF:

0.436

Gnomad4 SAS exome

AF:

0.332

Gnomad4 FIN exome

AF:

0.399

Gnomad4 NFE exome

AF:

0.336

Gnomad4 OTH exome

AF:

0.314

GnomAD4 genome

AF:

0.283

AC:

42202

AN:

149326

Hom.:

6599

Cov.:

AF XY:

0.286

AC XY:

20857

AN XY:

72826

show subpopulations

Gnomad4 AFR

AF:

0.137

Gnomad4 AMR

AF:

0.289

Gnomad4 ASJ

AF:

0.296

Gnomad4 EAS

AF:

0.359

Gnomad4 SAS

AF:

0.351

Gnomad4 FIN

AF:

0.401

Gnomad4 NFE

AF:

0.341

Gnomad4 OTH

AF:

0.288

Alfa

AF:

0.203

Hom.:

505

Bravo

AF:

0.270

Asia WGS

AF:

0.369

AC:

1201

AN:

3264

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Nephronophthisis 16

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

ANKS6-related disorder

Benign:1

Benign, no assertion criteria provided

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

-0.59

CADD

Benign

DANN

Benign

0.93

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.2

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