rs34796699

Positions:

• chr10-60196628-GAA-G
• chr10-60196628-GAA-GA
• chr10-60196628-GAA-GAAA
• chr10-60196628-GAA-GAAAA
• chr10-60196628-GAA-GAAAAA
• chr10-60196628-GAA-GAAAAAA
• chr10-60196628-GAA-GAAAAAAA

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP6

The NM_020987.5(ANK3):​c.1690-5_1690-4delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000134 in 1,258,120 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000038 (0 hom., cov: 28)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: ANK3 NM_020987.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.907

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 10-60196628-GAA-G is Benign according to our data. Variant chr10-60196628-GAA-G is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANK3	NM_020987.5	c.1690-5_1690-4delTT		splice_region_variant, intron_variant		ENST00000280772.7	NP_066267.2
ANK3	NM_001204404.2	c.1639-5_1639-4delTT		splice_region_variant, intron_variant			NP_001191333.1
ANK3	NM_001320874.2	c.1690-5_1690-4delTT		splice_region_variant, intron_variant			NP_001307803.1
ANK3	NM_001204403.2	c.1672-5_1672-4delTT		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.1690-5_1690-4delTT		splice_region_variant, intron_variant		1	NM_020987.5	ENSP00000280772.1

Frequencies

GnomAD3 genomes AF: 0.0000376 AC: 5 AN: 133090 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.000108

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: 0.0000164

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000146 AC: 164 AN: 1125030 Hom.: 0 AF XY: 0.000138 AC XY: 78 AN XY: 564094

Gnomad4 AFR exome AF: 0.000115

Gnomad4 AMR exome AF: 0.0000915

Gnomad4 ASJ exome AF: 0.000143

Gnomad4 EAS exome AF: 0.0000596

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.000188

Gnomad4 NFE exome AF: 0.000157

Gnomad4 OTH exome AF: 0.000106

GnomAD4 genome AF: 0.0000376 AC: 5 AN: 133090 Hom.: 0 Cov.: 28 AF XY: 0.0000470 AC XY: 3 AN XY: 63810

Gnomad4 AFR AF: 0.000108

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: 0.0000164

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

Other links and lift over

dbSNP: rs34796699; hg19: chr10-61956386;