chr10-60540625-A-G

Variant summary

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

The ENST00000373827.6(ANK3):​c.96+74561T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.088 in 151,918 control chromosomes in the GnomAD database, including 1,147 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 0.088 ( 1147 hom., cov: 32)

Consequence

ANK3
ENST00000373827.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.85
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=-0.87).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ANK3NM_001204403.2 linkuse as main transcriptc.96+74561T>C intron_variant NP_001191332.1
ANK3NM_001204404.2 linkuse as main transcriptc.63+31840T>C intron_variant NP_001191333.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ANK3ENST00000373827.6 linkuse as main transcriptc.96+74561T>C intron_variant 1 ENSP00000362933 Q12955-5
ANK3ENST00000503366.6 linkuse as main transcriptc.63+31840T>C intron_variant 2 ENSP00000425236 Q12955-4
ANK3ENST00000622427.4 linkuse as main transcriptc.63+31840T>C intron_variant, NMD_transcript_variant 2 ENSP00000483244
ANK3ENST00000510382.1 linkuse as main transcriptn.102-32000T>C intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.0880
AC:
13363
AN:
151800
Hom.:
1142
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0168
Gnomad AMI
AF:
0.00329
Gnomad AMR
AF:
0.203
Gnomad ASJ
AF:
0.0785
Gnomad EAS
AF:
0.310
Gnomad SAS
AF:
0.171
Gnomad FIN
AF:
0.194
Gnomad MID
AF:
0.0443
Gnomad NFE
AF:
0.0687
Gnomad OTH
AF:
0.0803
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0880
AC:
13368
AN:
151918
Hom.:
1147
Cov.:
32
AF XY:
0.0980
AC XY:
7277
AN XY:
74250
show subpopulations
Gnomad4 AFR
AF:
0.0167
Gnomad4 AMR
AF:
0.204
Gnomad4 ASJ
AF:
0.0785
Gnomad4 EAS
AF:
0.309
Gnomad4 SAS
AF:
0.168
Gnomad4 FIN
AF:
0.194
Gnomad4 NFE
AF:
0.0687
Gnomad4 OTH
AF:
0.0814
Alfa
AF:
0.0950
Hom.:
754
Bravo
AF:
0.0884
Asia WGS
AF:
0.248
AC:
860
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
0.49
DANN
Benign
0.65

Splicing

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: rs1938526; hg19: chr10-62300383; API