Genetic Variant ANKRD6:p.Thr176Asn (chr6-89613802-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001242809.2(ANKRD6):c.527C>A(p.Thr176Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00016 in 1,614,010 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 1 hom. )

Consequence

ANKRD6
NM_001242809.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.33

Publications

2 publications found

Variant links:

Genes affected

ANKRD6 (HGNC:17280): (ankyrin repeat domain 6) Predicted to be involved in negative regulation of canonical Wnt signaling pathway and positive regulation of JNK cascade. Predicted to act upstream of or within positive regulation of Wnt signaling pathway, planar cell polarity pathway. Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

ANKRD6 links:

LYRM2 (HGNC:25229): (LYR motif containing 2)

LYRM2 links:

LOC124901359 (HGNC:):

LOC124901359 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242809.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKRD6	NM_001242809.2	MANE Select	c.527C>A	p.Thr176Asn	missense	Exon 7 of 16	NP_001229738.1	Q9Y2G4-2
ANKRD6	NM_001242811.1		c.527C>A	p.Thr176Asn	missense	Exon 7 of 16	NP_001229740.1	Q9Y2G4-2
ANKRD6	NM_014942.4		c.527C>A	p.Thr176Asn	missense	Exon 7 of 16	NP_055757.3	Q9Y2G4-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKRD6	ENST00000339746.9	TSL:1 MANE Select	c.527C>A	p.Thr176Asn	missense	Exon 7 of 16	ENSP00000345767.4	Q9Y2G4-2
ANKRD6	ENST00000447838.6	TSL:1	c.527C>A	p.Thr176Asn	missense	Exon 7 of 16	ENSP00000396771.2	Q9Y2G4-3
ANKRD6	ENST00000369408.9	TSL:1	c.527C>A	p.Thr176Asn	missense	Exon 7 of 15	ENSP00000358416.5	Q9Y2G4-1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000735

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000157

AC:

AN:

249070

AF XY:

0.000170

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000172

AC:

252

AN:

1461660

Hom.:

Cov.:

AF XY:

0.000179

AC XY:

130

AN XY:

727114

show subpopulations

African (AFR)

AF:

0.0000597

AC:

AN:

33480

American (AMR)

AF:

0.0000447

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.000800

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.000131

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000139

AC:

154

AN:

1111852

Other (OTH)

AF:

0.000248

AC:

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000459

AC:

AN:

152350

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.0000240

AC:

AN:

41580

American (AMR)

AF:

0.00

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68032

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.0000642

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000149

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.50

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.097

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.069

MetaRNN

Uncertain

0.70

MetaSVM

Uncertain

0.097

MutationAssessor

Benign

1.5

PhyloP100

5.3

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-3.9

REVEL

Uncertain

0.54

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0040

Polyphen

0.99

Vest4

0.91

MVP

0.88

MPC

0.34

ClinPred

0.30

GERP RS

4.7

Varity_R

0.76

gMVP

0.74

Mutation Taster

=38/62

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over