chr10-60074815-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_020987.5(ANK3):​c.6066C>T​(p.Ala2022Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0921 in 1,613,714 control chromosomes in the GnomAD database, including 7,857 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.072 ( 541 hom., cov: 32)
Exomes 𝑓: 0.094 ( 7316 hom. )

Consequence

ANK3
NM_020987.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.840
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
Variant 10-60074815-G-A is Benign according to our data. Variant chr10-60074815-G-A is described in ClinVar as [Benign]. Clinvar id is 128373.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.84 with no splicing effect.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ANK3NM_020987.5 linkuse as main transcriptc.6066C>T p.Ala2022Ala synonymous_variant 37/44 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.6066C>T p.Ala2022Ala synonymous_variant 37/441 NM_020987.5 ENSP00000280772.1 Q12955-3

Frequencies

GnomAD3 genomes
AF:
0.0718
AC:
10923
AN:
152054
Hom.:
541
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0200
Gnomad AMI
AF:
0.0779
Gnomad AMR
AF:
0.0727
Gnomad ASJ
AF:
0.0573
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.0172
Gnomad FIN
AF:
0.0778
Gnomad MID
AF:
0.0728
Gnomad NFE
AF:
0.112
Gnomad OTH
AF:
0.0767
GnomAD3 exomes
AF:
0.0720
AC:
18023
AN:
250472
Hom.:
911
AF XY:
0.0724
AC XY:
9796
AN XY:
135308
show subpopulations
Gnomad AFR exome
AF:
0.0177
Gnomad AMR exome
AF:
0.0510
Gnomad ASJ exome
AF:
0.0617
Gnomad EAS exome
AF:
0.000218
Gnomad SAS exome
AF:
0.0210
Gnomad FIN exome
AF:
0.0820
Gnomad NFE exome
AF:
0.109
Gnomad OTH exome
AF:
0.0953
GnomAD4 exome
AF:
0.0942
AC:
137697
AN:
1461542
Hom.:
7316
Cov.:
36
AF XY:
0.0925
AC XY:
67215
AN XY:
727040
show subpopulations
Gnomad4 AFR exome
AF:
0.0152
Gnomad4 AMR exome
AF:
0.0544
Gnomad4 ASJ exome
AF:
0.0633
Gnomad4 EAS exome
AF:
0.000202
Gnomad4 SAS exome
AF:
0.0214
Gnomad4 FIN exome
AF:
0.0855
Gnomad4 NFE exome
AF:
0.109
Gnomad4 OTH exome
AF:
0.0855
GnomAD4 genome
AF:
0.0717
AC:
10917
AN:
152172
Hom.:
541
Cov.:
32
AF XY:
0.0673
AC XY:
5002
AN XY:
74370
show subpopulations
Gnomad4 AFR
AF:
0.0199
Gnomad4 AMR
AF:
0.0727
Gnomad4 ASJ
AF:
0.0573
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.0168
Gnomad4 FIN
AF:
0.0778
Gnomad4 NFE
AF:
0.112
Gnomad4 OTH
AF:
0.0759
Alfa
AF:
0.0961
Hom.:
1084
Bravo
AF:
0.0687
Asia WGS
AF:
0.0160
AC:
56
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 30, 2024- -
not specified Benign:1
Likely benign, no assertion criteria providedclinical testingGenetic Services Laboratory, University of Chicago-Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
ANK3-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesNov 25, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
6.1
DANN
Benign
0.66

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: rs17208576; hg19: chr10-61834573; COSMIC: COSV55050214; COSMIC: COSV55050214; API