dbSNP rs142778119: ANK3:c.13065+20G>A (chr10-60055638-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_020987.5(ANK3):c.13065+20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000846 in 1,578,694 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0044 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00047 ( 7 hom. )

Consequence

ANK3
NM_020987.5 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.05

Publications

0 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: Orphanet, Labcorp Genetics (formerly Invitae), 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 10-60055638-C-T is Benign according to our data. Variant chr10-60055638-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 446050.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00439 (669/152278) while in subpopulation AFR AF = 0.0147 (611/41560). AF 95% confidence interval is 0.0137. There are 2 homozygotes in GnomAd4. There are 303 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR,Unknown,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020987.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ANK3	NM_020987.5	MANE Select	c.13065+20G>A	intron	N/A	NP_066267.2
ANK3	NM_001204404.2		c.5538+20G>A	intron	N/A	NP_001191333.1	Q12955-4
ANK3	NM_001320874.2		c.5535+20G>A	intron	N/A	NP_001307803.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ANK3	ENST00000280772.7	TSL:1 MANE Select	c.13065+20G>A	intron	N/A	ENSP00000280772.1	Q12955-3
ANK3	ENST00000373827.6	TSL:1	c.5517+20G>A	intron	N/A	ENSP00000362933.2	Q12955-5
ANK3	ENST00000355288.6	TSL:1	c.2937+20G>A	intron	N/A	ENSP00000347436.2	Q12955-6

Frequencies

GnomAD3 genomes

AF:

0.00440

AC:

670

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0148

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00383

GnomAD2 exomes

AF:

0.00121

AC:

270

AN:

223888

AF XY:

0.000876

show subpopulations

Gnomad AFR exome

AF:

0.0158

Gnomad AMR exome

AF:

0.000496

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000573

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000468

AC:

667

AN:

1426416

Hom.:

Cov.:

AF XY:

0.000414

AC XY:

293

AN XY:

707448

show subpopulations

African (AFR)

AF:

0.0158

AC:

502

AN:

31676

American (AMR)

AF:

0.000695

AC:

AN:

37426

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23752

East Asian (EAS)

AF:

0.0000254

AC:

AN:

39430

South Asian (SAS)

AF:

0.0000623

AC:

AN:

80300

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52288

Middle Eastern (MID)

AF:

0.00143

AC:

AN:

4880

European-Non Finnish (NFE)

AF:

0.0000474

AC:

AN:

1098038

Other (OTH)

AF:

0.00126

AC:

AN:

58626

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

102

136

170

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

GnomAD4 genome

AF:

0.00439

AC:

669

AN:

152278

Hom.:

Cov.:

AF XY:

0.00407

AC XY:

303

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0147

AC:

611

AN:

41560

American (AMR)

AF:

0.00255

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68024

Other (OTH)

AF:

0.00379

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

103

137

171

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:

0.00279

Hom.:

Bravo

AF:

0.00541

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.35

(source)

DANN

Benign

0.72

PhyloP100

-1.1

PromoterAI

-0.10

Neutral

(source)

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

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