NM_173551.5:c.238A>G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_173551.5(ANKS6):c.238A>G(p.Thr80Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ANKS6
NM_173551.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.84

Publications

0 publications found

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]

ANKS6 Gene-Disease associations (from GenCC):

nephronophthisis 16
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
nephronophthisis 1
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
nephronophthisis 2
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ANKS6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3932194).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKS6	NM_173551.5 link	c.238A>G	p.Thr80Ala	missense_variant	Exon 1 of 15	ENST00000353234.5	NP_775822.3	Q68DC2-1B3KXP1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ANKS6	ENST00000353234.5 link	c.238A>G	p.Thr80Ala	missense_variant	Exon 1 of 15	1	NM_173551.5	ENSP00000297837.6	Q68DC2-1
ANKS6	ENST00000471846.1 link	n.286A>G		non_coding_transcript_exon_variant	Exon 1 of 2	2
ANKS6	ENST00000375019.6 link	c.-42+430A>G		intron_variant	Intron 1 of 14	5		ENSP00000364159.2	A0A0A0MRS7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1229404

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

601196

African (AFR)

AF:

0.00

AC:

AN:

25522

American (AMR)

AF:

0.00

AC:

AN:

21174

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20508

East Asian (EAS)

AF:

0.00

AC:

AN:

27090

South Asian (SAS)

AF:

0.00

AC:

AN:

56544

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29786

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3546

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

995380

Other (OTH)

AF:

0.00

AC:

AN:

49854

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Nephronophthisis 16

Uncertain:1

Jun 13, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 80 of the ANKS6 protein (p.Thr80Ala). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ANKS6-related conditions. ClinVar contains an entry for this variant (Variation ID: 474450). 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: "Deleterious"; PolyPhen-2: "Possibly 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

0.53

BayesDel_addAF

Uncertain

0.020

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.14

Eigen

Benign

0.094

Eigen_PC

Benign

0.081

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.86

M_CAP

Pathogenic

0.72

MetaRNN

Benign

0.39

MetaSVM

Benign

-0.66

MutationAssessor

Uncertain

2.3

PhyloP100

2.8

PrimateAI

Pathogenic

0.95

PROVEAN

Uncertain

-3.5

REVEL

Uncertain

0.31

Sift

Uncertain

0.0080

Sift4G

Benign

0.061

Polyphen

0.51

Vest4

0.33

MutPred

0.69

Loss of glycosylation at T80 (P = 0.0323);

MVP

0.73

MPC

0.39

ClinPred

0.98

GERP RS

3.0

PromoterAI

-0.00060

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.28

gMVP

0.61

Mutation Taster

=58/42

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over