rs72818458

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020987.5(ANK3):​c.*19+2542A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0634 in 152,280 control chromosomes in the GnomAD database, including 423 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 0.063 ( 423 hom., cov: 32)

Consequence

ANK3
NM_020987.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0740
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0957 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ANK3NM_020987.5 linkuse as main transcriptc.*19+2542A>T intron_variant ENST00000280772.7 NP_066267.2 Q12955-3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ANK3ENST00000280772.7 linkuse as main transcriptc.*19+2542A>T intron_variant 1 NM_020987.5 ENSP00000280772.1 Q12955-3

Frequencies

GnomAD3 genomes
AF:
0.0635
AC:
9669
AN:
152162
Hom.:
423
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0176
Gnomad AMI
AF:
0.0725
Gnomad AMR
AF:
0.0633
Gnomad ASJ
AF:
0.0619
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.0195
Gnomad FIN
AF:
0.0736
Gnomad MID
AF:
0.0949
Gnomad NFE
AF:
0.0977
Gnomad OTH
AF:
0.0684
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0634
AC:
9661
AN:
152280
Hom.:
423
Cov.:
32
AF XY:
0.0604
AC XY:
4494
AN XY:
74460
show subpopulations
Gnomad4 AFR
AF:
0.0175
Gnomad4 AMR
AF:
0.0632
Gnomad4 ASJ
AF:
0.0619
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.0193
Gnomad4 FIN
AF:
0.0736
Gnomad4 NFE
AF:
0.0977
Gnomad4 OTH
AF:
0.0676
Alfa
AF:
0.0873
Hom.:
79
Bravo
AF:
0.0605
Asia WGS
AF:
0.0140
AC:
47
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.59
CADD
Benign
8.0
DANN
Benign
0.90

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs72818458; hg19: chr10-61799888; API