Variant rs6415847 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_173551.5(ANKS6):c.1930G>C(p.Val644Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000209 in 1,434,246 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ANKS6
NM_173551.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.31

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.053862035).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKS6	NM_173551.5 linkuse as main transcript	c.1930G>C	p.Val644Leu	missense_variant	10/15	ENST00000353234.5	NP_775822.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKS6	ENST00000353234.5 linkuse as main transcript	c.1930G>C	p.Val644Leu	missense_variant	10/15	1	NM_173551.5	ENSP00000297837	P1	Q68DC2-1
ANKS6	ENST00000375019.6 linkuse as main transcript	c.1027G>C	p.Val343Leu	missense_variant	9/15	5		ENSP00000364159
ANKS6	ENST00000444472.5 linkuse as main transcript	c.337G>C	p.Val113Leu	missense_variant	3/9	2		ENSP00000398648
ANKS6	ENST00000634393.1 linkuse as main transcript	n.1030G>C		non_coding_transcript_exon_variant	8/15	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000131

AC:

AN:

229872

Hom.:

AF XY:

0.0000240

AC XY:

AN XY:

124798

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:

0.000112

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000209

AC:

AN:

1434246

Hom.:

Cov.:

AF XY:

0.00000421

AC XY:

AN XY:

712346

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000368

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000166

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.40

CADD

Benign

4.7

DANN

Benign

0.97

DEOGEN2

Benign

0.013

.;T

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.054

T;T

MetaSVM

Benign

-0.76

MutationAssessor

Benign

1.4

.;L

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.92

N;N

REVEL

Benign

0.024

Sift

Benign

0.36

T;T

Sift4G

Benign

0.57

T;T

Polyphen

0.0070

.;B

Vest4

0.17

MutPred

0.17

.;Loss of sheet (P = 0.0457);

MVP

0.59

MPC

0.11

ClinPred

0.054

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.032

gMVP

0.19

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