Variant 10-60196628-GAA-GAAAAAAA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020987.5(ANK3):c.1690-4_1690-3insTTTTT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000169 in 1,127,566 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 28)

Exomes 𝑓: 0.000017 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ANK3
NM_020987.5 splice_region, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.469

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
ANK3	NM_020987.5 linkuse as main transcript	c.1690-4_1690-3insTTTTT	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000280772.7
ANK3	NM_001204403.2 linkuse as main transcript	c.1672-4_1672-3insTTTTT	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
ANK3	NM_001204404.2 linkuse as main transcript	c.1639-4_1639-3insTTTTT	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
ANK3	NM_001320874.2 linkuse as main transcript	c.1690-4_1690-3insTTTTT	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANK3	ENST00000280772.7 linkuse as main transcript	c.1690-4_1690-3insTTTTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_020987.5		Q12955-3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

133090

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000169

AC:

AN:

1127566

Hom.:

Cov.:

AF XY:

0.0000177

AC XY:

AN XY:

565306

show subpopulations

Gnomad4 AFR exome

AF:

0.000268

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000476

Gnomad4 EAS exome

AF:

0.000119

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000268

Gnomad4 NFE exome

AF:

0.00000467

Gnomad4 OTH exome

AF:

0.0000211

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

133090

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

63810

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over