Menu
GeneBe

rs138948716

chr9-98796327-G-Achr9-98796327-G-Cchr9-98796327-G-T

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.Ala55=) 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

2

Clinical Significance

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

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.419 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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 UniProt
ANKS6NM_173551.5 linkuse as main transcriptc.165C>T p.Ala55= synonymous_variant 1/15 ENST00000353234.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ANKS6ENST00000353234.5 linkuse as main transcriptc.165C>T p.Ala55= synonymous_variant 1/151 NM_173551.5 P1Q68DC2-1
ANKS6ENST00000375019.6 linkuse as main transcriptc.-42+357C>T intron_variant 5
ANKS6ENST00000471846.1 linkuse as main transcriptn.213C>T non_coding_transcript_exon_variant 1/22

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.283
AC:
42190
AN:
149218
Hom.:
6594
Cov.:
33
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.:
89
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.:
32
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.283
AC:
42202
AN:
149326
Hom.:
6599
Cov.:
33
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:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Nephronophthisis 16 Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 31, 2024- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxNov 10, 2018- -
ANKS6-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesSep 26, 2022This 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
13
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.

Other links and lift over

dbSNP: rs138948716; hg19: chr9-101558609; COSMIC: COSV62050829; COSMIC: COSV62050829; API