rs117138204

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_020987.5(ANK3):c.1047C>T(p.Cys349Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00634 in 1,614,104 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0057 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0064 ( 55 hom. )

Consequence

ANK3
NM_020987.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.184

Publications

2 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 10-60208183-G-A is Benign according to our data. Variant chr10-60208183-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 210139.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.184 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00567 (864/152296) while in subpopulation AMR AF = 0.00713 (109/15294). AF 95% confidence interval is 0.00604. There are 4 homozygotes in GnomAd4. There are 380 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 4 AR,Unknown,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANK3	NM_020987.5 link	c.1047C>T	p.Cys349Cys	synonymous_variant	Exon 10 of 44	ENST00000280772.7	NP_066267.2	Q12955-3
ANK3	NM_001204404.2 link	c.996C>T	p.Cys332Cys	synonymous_variant	Exon 10 of 44		NP_001191333.1	Q12955-4
ANK3	NM_001320874.2 link	c.1047C>T	p.Cys349Cys	synonymous_variant	Exon 10 of 43		NP_001307803.1
ANK3	NM_001204403.2 link	c.1029C>T	p.Cys343Cys	synonymous_variant	Exon 11 of 44		NP_001191332.1	Q12955-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANK3	ENST00000280772.7 link	c.1047C>T	p.Cys349Cys	synonymous_variant	Exon 10 of 44	1	NM_020987.5	ENSP00000280772.1		Q12955-3

Frequencies

GnomAD3 genomes

AF:

0.00566

AC:

862

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00456

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00720

Gnomad ASJ

AF:

0.0225

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00292

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00636

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00630

AC:

1583

AN:

251074

AF XY:

0.00620

show subpopulations

Gnomad AFR exome

AF:

0.00388

Gnomad AMR exome

AF:

0.00515

Gnomad ASJ exome

AF:

0.0230

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00388

Gnomad NFE exome

AF:

0.00793

Gnomad OTH exome

AF:

0.00800

GnomAD4 exome

AF:

0.00641

AC:

9367

AN:

1461808

Hom.:

Cov.:

AF XY:

0.00634

AC XY:

4613

AN XY:

727220

show subpopulations

African (AFR)

AF:

0.00388

AC:

130

AN:

33472

American (AMR)

AF:

0.00494

AC:

221

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0210

AC:

550

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00265

AC:

229

AN:

86258

European-Finnish (FIN)

AF:

0.00301

AC:

161

AN:

53416

Middle Eastern (MID)

AF:

0.00798

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00678

AC:

7536

AN:

1111946

Other (OTH)

AF:

0.00818

AC:

494

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

478

956

1433

1911

2389

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

274

548

822

1096

1370

<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:

0.00567

AC:

864

AN:

152296

Hom.:

Cov.:

AF XY:

0.00510

AC XY:

380

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.00464

AC:

193

AN:

41572

American (AMR)

AF:

0.00713

AC:

109

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0225

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00166

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00292

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00637

AC:

433

AN:

68026

Other (OTH)

AF:

0.00473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

121

161

201

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

100

<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:

0.00703

Hom.:

Bravo

AF:

0.00586

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00654

EpiControl

AF:

0.00836

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 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 -

not specified

Benign:1

Jan 19, 2018

Genetic Services Laboratory, University of Chicago

Significance: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

-0.39

CADD

Benign

8.8

(source)

DANN

Benign

0.60

PhyloP100

-0.18

Mutation Taster

=79/21

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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