rs200644058
Positions:
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_173551.5(ANKS6):āc.2564T>Cā(p.Phe855Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00106 in 1,613,736 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.00078 ( 0 hom., cov: 32)
Exomes š: 0.0011 ( 1 hom. )
Consequence
ANKS6
NM_173551.5 missense
NM_173551.5 missense
Scores
5
9
3
Clinical Significance
Conservation
PhyloP100: 8.65
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 Likely_benign. Variant got -3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.033640146).
BP6
?
Variant 9-98736571-A-G is Benign according to our data. Variant chr9-98736571-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 474451.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=2}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANKS6 | NM_173551.5 | c.2564T>C | p.Phe855Ser | missense_variant | 15/15 | ENST00000353234.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANKS6 | ENST00000353234.5 | c.2564T>C | p.Phe855Ser | missense_variant | 15/15 | 1 | NM_173551.5 | P1 | |
ANKS6 | ENST00000375019.6 | c.1661T>C | p.Phe554Ser | missense_variant | 14/15 | 5 | |||
ANKS6 | ENST00000444472.5 | c.974T>C | p.Phe325Ser | missense_variant | 8/9 | 2 | |||
ANKS6 | ENST00000634393.1 | n.1699T>C | non_coding_transcript_exon_variant | 14/15 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000776 AC: 118AN: 152140Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
118
AN:
152140
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00111 AC: 274AN: 247358Hom.: 0 AF XY: 0.00104 AC XY: 140AN XY: 134356
GnomAD3 exomes
AF:
AC:
274
AN:
247358
Hom.:
AF XY:
AC XY:
140
AN XY:
134356
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00109 AC: 1598AN: 1461480Hom.: 1 Cov.: 32 AF XY: 0.00106 AC XY: 770AN XY: 726986
GnomAD4 exome
AF:
AC:
1598
AN:
1461480
Hom.:
Cov.:
32
AF XY:
AC XY:
770
AN XY:
726986
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000775 AC: 118AN: 152256Hom.: 0 Cov.: 32 AF XY: 0.000712 AC XY: 53AN XY: 74442
GnomAD4 genome
?
AF:
AC:
118
AN:
152256
Hom.:
Cov.:
32
AF XY:
AC XY:
53
AN XY:
74442
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
5
ALSPAC
AF:
AC:
4
ESP6500AA
AF:
AC:
1
ESP6500EA
AF:
AC:
10
ExAC
?
AF:
AC:
206
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2022 | - - |
Nephronophthisis 16 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
ANKS6-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 03, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Pathogenic
D;D
Sift4G
Benign
T;T
Polyphen
1.0
.;D
Vest4
MVP
MPC
0.69
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at