chr9-98756543-G-C
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_173551.5(ANKS6):c.2203C>G(p.Pro735Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00191 in 1,593,224 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0088 ( 20 hom., cov: 31)
Exomes 𝑓: 0.0012 ( 23 hom. )
Consequence
ANKS6
NM_173551.5 missense
NM_173551.5 missense
Scores
2
6
8
Clinical Significance
Conservation
PhyloP100: 7.38
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 Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0077734888).
BP6
?
Variant 9-98756543-G-C is Benign according to our data. Variant chr9-98756543-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 262848.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-98756543-G-C is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00879 (1338/152270) while in subpopulation AFR AF= 0.0302 (1254/41548). AF 95% confidence interval is 0.0288. There are 20 homozygotes in gnomad4. There are 653 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 20 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANKS6 | NM_173551.5 | c.2203C>G | p.Pro735Ala | missense_variant | 12/15 | ENST00000353234.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANKS6 | ENST00000353234.5 | c.2203C>G | p.Pro735Ala | missense_variant | 12/15 | 1 | NM_173551.5 | P1 | |
ANKS6 | ENST00000375019.6 | c.1300C>G | p.Pro434Ala | missense_variant | 11/15 | 5 | |||
ANKS6 | ENST00000444472.5 | c.613C>G | p.Pro205Ala | missense_variant | 5/9 | 2 | |||
ANKS6 | ENST00000634393.1 | n.1303C>G | non_coding_transcript_exon_variant | 10/15 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00877 AC: 1335AN: 152152Hom.: 20 Cov.: 31
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00236 AC: 528AN: 223366Hom.: 6 AF XY: 0.00179 AC XY: 217AN XY: 120988
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GnomAD4 exome AF: 0.00119 AC: 1710AN: 1440954Hom.: 23 Cov.: 31 AF XY: 0.00103 AC XY: 737AN XY: 715990
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GnomAD4 genome ? AF: 0.00879 AC: 1338AN: 152270Hom.: 20 Cov.: 31 AF XY: 0.00877 AC XY: 653AN XY: 74454
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ESP6500AA
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Asia WGS
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3478
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Nephronophthisis 16 Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Mar 09, 2022 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 26, 2020 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Benign
D;T
Sift4G
Benign
T;D
Polyphen
1.0
.;D
Vest4
MVP
MPC
0.51
ClinPred
T
GERP RS
Varity_R
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