chr9-98745567-C-T

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

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.57
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 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
ANKS6NM_173551.5 linkuse as main transcriptc.2503G>A p.Ala835Thr missense_variant 14/15 ENST00000353234.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ANKS6ENST00000353234.5 linkuse as main transcriptc.2503G>A p.Ala835Thr missense_variant 14/151 NM_173551.5 P1Q68DC2-1
ANKS6ENST00000375019.6 linkuse as main transcriptc.1600G>A p.Ala534Thr missense_variant 13/155
ANKS6ENST00000444472.5 linkuse as main transcriptc.913G>A p.Ala305Thr missense_variant 7/92
ANKS6ENST00000634393.1 linkuse as main transcriptn.1638G>A non_coding_transcript_exon_variant 13/155

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152194
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000401
AC:
10
AN:
249566
Hom.:
1
AF XY:
0.0000517
AC XY:
7
AN XY:
135394
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000981
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000618
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000219
AC:
32
AN:
1460494
Hom.:
1
Cov.:
30
AF XY:
0.0000261
AC XY:
19
AN XY:
726708
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000252
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152194
Hom.:
0
Cov.:
32
AF XY:
0.0000672
AC XY:
5
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000711
Hom.:
0
Bravo
AF:
0.0000264
ExAC
AF:
0.0000331
AC:
4

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 submitterclinical testingInvitaeDec 11, 2018This 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.37
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.27
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.011
.;T
Eigen
Benign
0.030
Eigen_PC
Benign
0.15
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Uncertain
0.90
D;D
M_CAP
Benign
0.033
D
MetaRNN
Benign
0.24
T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
0.47
.;N
MutationTaster
Benign
0.97
D;D;D;D
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
-1.0
N;N
REVEL
Benign
0.25
Sift
Benign
0.28
T;T
Sift4G
Benign
0.46
T;T
Polyphen
0.98
.;D
Vest4
0.36
MVP
0.80
MPC
0.51
ClinPred
0.48
T
GERP RS
4.8
Varity_R
0.29
gMVP
0.39

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.11
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: rs765164797; hg19: chr9-101507849; COSMIC: COSV62049329; API