Variant chr9-98756549-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_173551.5(ANKS6):c.2197A>G(p.Thr733Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000756 in 1,587,642 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T733P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000070 ( 0 hom. )

Consequence

ANKS6
NM_173551.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.36

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKS6	NM_173551.5 linkuse as main transcript	c.2197A>G	p.Thr733Ala	missense_variant	12/15	ENST00000353234.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKS6	ENST00000353234.5 linkuse as main transcript	c.2197A>G	p.Thr733Ala	missense_variant	12/15	1	NM_173551.5	P1	Q68DC2-1
ANKS6	ENST00000375019.6 linkuse as main transcript	c.1294A>G	p.Thr432Ala	missense_variant	11/15	5
ANKS6	ENST00000444472.5 linkuse as main transcript	c.607A>G	p.Thr203Ala	missense_variant	5/9	2
ANKS6	ENST00000634393.1 linkuse as main transcript	n.1297A>G		non_coding_transcript_exon_variant	10/15	5

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151994

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000908

AC:

AN:

220312

Hom.:

AF XY:

0.00000839

AC XY:

AN XY:

119152

show subpopulations

Gnomad AFR exome

AF:

0.0000686

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000403

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000697

AC:

AN:

1435648

Hom.:

Cov.:

AF XY:

0.0000112

AC XY:

AN XY:

712850

show subpopulations

Gnomad4 AFR exome

AF:

0.0000311

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000123

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000726

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151994

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74234

show subpopulations

Gnomad4 AFR

AF:

0.0000242

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.00000827

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Benign

-0.069

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.044

.;T

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.85

T;D

M_CAP

Benign

0.075

MetaRNN

Uncertain

0.46

T;T

MetaSVM

Uncertain

-0.081

MutationAssessor

Benign

0.81

.;L

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-2.2

N;N

REVEL

Benign

0.20

Sift

Uncertain

0.019

D;T

Sift4G

Uncertain

0.030

D;D

Polyphen

0.99

.;D

Vest4

0.77

MutPred

0.19

.;Loss of glycosylation at T733 (P = 0.0265);

MVP

0.78

MPC

0.24

ClinPred

0.52

GERP RS

5.4

Varity_R

0.34

gMVP

0.41

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over