chr9-98745567-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_173551.5(ANKS6):c.2503G>A(p.Ala835Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000236 in 1,612,688 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000022 ( 1 hom. )
Consequence
ANKS6
NM_173551.5 missense
NM_173551.5 missense
Scores
1
4
14
Clinical Significance
Conservation
PhyloP100: 5.57
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.24023375).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANKS6 | NM_173551.5 | c.2503G>A | p.Ala835Thr | missense_variant | 14/15 | ENST00000353234.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANKS6 | ENST00000353234.5 | c.2503G>A | p.Ala835Thr | missense_variant | 14/15 | 1 | NM_173551.5 | P1 | |
ANKS6 | ENST00000375019.6 | c.1600G>A | p.Ala534Thr | missense_variant | 13/15 | 5 | |||
ANKS6 | ENST00000444472.5 | c.913G>A | p.Ala305Thr | missense_variant | 7/9 | 2 | |||
ANKS6 | ENST00000634393.1 | n.1638G>A | non_coding_transcript_exon_variant | 13/15 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152194Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000401 AC: 10AN: 249566Hom.: 1 AF XY: 0.0000517 AC XY: 7AN XY: 135394
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GnomAD4 exome AF: 0.0000219 AC: 32AN: 1460494Hom.: 1 Cov.: 30 AF XY: 0.0000261 AC XY: 19AN XY: 726708
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GnomAD4 genome AF: 0.0000394 AC: 6AN: 152194Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74350
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Nephronophthisis 16 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 11, 2018 | This sequence change replaces alanine with threonine at codon 835 of the ANKS6 protein (p.Ala835Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs765164797, ExAC 0.01%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals with ANKS6-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;N
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
0.98
.;D
Vest4
MVP
MPC
0.51
ClinPred
T
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at