Genetic Variant ANK3:c.57+48199A>G (chr10-60685064-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000373827.6(ANK3):c.57+48199A>G variant causes a intron change. The variant allele was found at a frequency of 0.319 in 1,335,330 control chromosomes in the GnomAD database, including 73,545 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.27 ( 6639 hom., cov: 33)

Exomes 𝑓: 0.33 ( 66906 hom. )

Consequence

ANK3
ENST00000373827.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.00

Publications

5 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 links:

ARL4AP1 (HGNC:17741): (ADP ribosylation factor like GTPase 4A pseudogene 1)

ARL4AP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

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

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARL4AP1		n.60685064T>C		intragenic_variant
ANK3	NM_001204403.2 link	c.57+48199A>G		intron_variant	Intron 1 of 43		NP_001191332.1	Q12955-5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
ANK3	ENST00000373827.6 link	c.57+48199A>G	intron_variant	Intron 1 of 43	1	ENSP00000362933.2	Q12955-5
ARL4AP1	ENST00000503220.1 link	n.560T>C	non_coding_transcript_exon_variant	Exon 1 of 1	6
ANK3	ENST00000510382.1 link	n.62+48199A>G	intron_variant	Intron 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.269

AC:

40936

AN:

152004

Hom.:

6638

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0920

Gnomad AMI

AF:

0.324

Gnomad AMR

AF:

0.380

Gnomad ASJ

AF:

0.357

Gnomad EAS

AF:

0.378

Gnomad SAS

AF:

0.484

Gnomad FIN

AF:

0.371

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.308

Gnomad OTH

AF:

0.259

GnomAD4 exome

AF:

0.326

AC:

385600

AN:

1183208

Hom.:

66906

Cov.:

AF XY:

0.331

AC XY:

197790

AN XY:

597762

show subpopulations

African (AFR)

AF:

0.0775

AC:

2093

AN:

27008

American (AMR)

AF:

0.482

AC:

18120

AN:

37630

Ashkenazi Jewish (ASJ)

AF:

0.345

AC:

7442

AN:

21552

East Asian (EAS)

AF:

0.398

AC:

12602

AN:

31696

South Asian (SAS)

AF:

0.490

AC:

38172

AN:

77916

European-Finnish (FIN)

AF:

0.355

AC:

16528

AN:

46582

Middle Eastern (MID)

AF:

0.326

AC:

1611

AN:

4938

European-Non Finnish (NFE)

AF:

0.308

AC:

273278

AN:

887122

Other (OTH)

AF:

0.323

AC:

15754

AN:

48764

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

12177

24354

36530

48707

60884

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.269

AC:

40959

AN:

152122

Hom.:

6639

Cov.:

AF XY:

0.279

AC XY:

20776

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.0921

AC:

3824

AN:

41520

American (AMR)

AF:

0.381

AC:

5822

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.357

AC:

1241

AN:

3472

East Asian (EAS)

AF:

0.378

AC:

1952

AN:

5164

South Asian (SAS)

AF:

0.483

AC:

2325

AN:

4812

European-Finnish (FIN)

AF:

0.371

AC:

3923

AN:

10572

Middle Eastern (MID)

AF:

0.272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.308

AC:

20954

AN:

67984

Other (OTH)

AF:

0.258

AC:

544

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1439

2877

4316

5754

7193

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.283

Hom.:

3534

Bravo

AF:

0.260

Asia WGS

AF:

0.414

AC:

1435

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.63

PhyloP100

4.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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chr10-60685064-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over