10-60196628-GAA-GAAAAAAA

Position:

• chr10-60196628-GAA-GAAAAAAA

Variant summary

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

The NM_020987.5(ANK3):​c.1690-8_1690-4dupTTTTT variant causes a splice region, 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, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.469

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANK3	NM_020987.5	c.1690-8_1690-4dupTTTTT		splice_region_variant, intron_variant		ENST00000280772.7	NP_066267.2
ANK3	NM_001204404.2	c.1639-8_1639-4dupTTTTT		splice_region_variant, intron_variant			NP_001191333.1
ANK3	NM_001320874.2	c.1690-8_1690-4dupTTTTT		splice_region_variant, intron_variant			NP_001307803.1
ANK3	NM_001204403.2	c.1672-8_1672-4dupTTTTT		splice_region_variant, intron_variant			NP_001191332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANK3	ENST00000280772.7	c.1690-8_1690-4dupTTTTT		splice_region_variant, intron_variant		1	NM_020987.5	ENSP00000280772.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 133090 Hom.: 0 Cov.: 28 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: 19 AN: 1127566 Hom.: 0 Cov.: 21 AF XY: 0.0000177 AC XY: 10 AN XY: 565306

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: 0 AN: 133090 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs34796699; hg19: chr10-61956386;