rs11815168

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_020987.5(ANK3):c.8508T>C(p.His2836His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0061 in 1,613,978 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0043 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0063 ( 42 hom. )

Consequence

ANK3
NM_020987.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0550

Publications

3 publications found

Variant links:

Genes affected

ANK3 (HGNC:494): (ankyrin 3) Ankyrins are a family of proteins that are believed to link the integral membrane proteins to the underlying spectrin-actin cytoskeleton and play key roles in activities such as cell motility, activation, proliferation, contact, and the maintenance of specialized membrane domains. Multiple isoforms of ankyrin with different affinities for various target proteins are expressed in a tissue-specific, developmentally regulated manner. Most ankyrins are typically composed of three structural domains: an amino-terminal domain containing multiple ankyrin repeats; a central region with a highly conserved spectrin binding domain; and a carboxy-terminal regulatory domain which is the least conserved and subject to variation. Ankyrin 3 is an immunologically distinct gene product from ankyrins 1 and 2, and was originally found at the axonal initial segment and nodes of Ranvier of neurons in the central and peripheral nervous systems. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Feb 2011]

ANK3 Gene-Disease associations (from GenCC):

intellectual disability-hypotonia-spasticity-sleep disorder syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
intellectual disability
Inheritance: AR, AD Classification: MODERATE, LIMITED Submitted by: ClinGen, Ambry Genetics
Tourette syndrome
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ANK3 links:

ENSG00000232682 (HGNC:):

ENSG00000232682 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 10-60072373-A-G is Benign according to our data. Variant chr10-60072373-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 210175.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.055 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00425 (648/152294) while in subpopulation NFE AF = 0.00672 (457/68028). AF 95% confidence interval is 0.00621. There are 6 homozygotes in GnomAd4. There are 276 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 6 AR,Unknown,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANK3	NM_020987.5 link	c.8508T>C	p.His2836His	synonymous_variant	Exon 37 of 44	ENST00000280772.7	NP_066267.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANK3	ENST00000280772.7 link	c.8508T>C	p.His2836His	synonymous_variant	Exon 37 of 44	1	NM_020987.5	ENSP00000280772.1

Frequencies

GnomAD3 genomes

AF:

0.00426

AC:

648

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.0592

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00372

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00672

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00423

AC:

1061

AN:

250542

AF XY:

0.00461

show subpopulations

Gnomad AFR exome

AF:

0.00129

Gnomad AMR exome

AF:

0.00200

Gnomad ASJ exome

AF:

0.00358

Gnomad EAS exome

AF:

0.000272

Gnomad FIN exome

AF:

0.000509

Gnomad NFE exome

AF:

0.00645

Gnomad OTH exome

AF:

0.00508

GnomAD4 exome

AF:

0.00629

AC:

9198

AN:

1461684

Hom.:

Cov.:

AF XY:

0.00620

AC XY:

4510

AN XY:

727150

show subpopulations

African (AFR)

AF:

0.00108

AC:

AN:

33446

American (AMR)

AF:

0.00226

AC:

101

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.00390

AC:

102

AN:

26122

East Asian (EAS)

AF:

0.000101

AC:

AN:

39692

South Asian (SAS)

AF:

0.00587

AC:

506

AN:

86216

European-Finnish (FIN)

AF:

0.000711

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.0111

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00718

AC:

7979

AN:

1111954

Other (OTH)

AF:

0.00609

AC:

368

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

571

1141

1712

2282

2853

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

296

592

888

1184

1480

<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:

0.00425

AC:

648

AN:

152294

Hom.:

Cov.:

AF XY:

0.00371

AC XY:

276

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.00156

AC:

AN:

41566

American (AMR)

AF:

0.00177

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00519

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00373

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000283

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00672

AC:

457

AN:

68028

Other (OTH)

AF:

0.00237

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

101

134

168

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:

0.00499

Hom.:

Bravo

AF:

0.00424

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00693

EpiControl

AF:

0.00664

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Sep 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ANK3: BP4, BP7, BS2

Jan 12, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:1

Jun 01, 2015

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

1.5

(source)

DANN

Benign

0.56

PhyloP100

-0.055

Mutation Taster

=100/0

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

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over