rs34796699

Variant names:

• chr10-60196628-GAAA-G
• rs34796699
• NM_020987.5:c.1690-6_1690-4delTTT

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020987.5(ANK3):​c.1690-6_1690-4delTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000266 in 1,127,480 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. 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: 0.0000027 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANK3 NM_020987.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.907
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• intellectual disability-hypotonia-spasticity-sleep disorder syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• intellectual disability

  Inheritance: AR, AD Classification: MODERATE, LIMITED Submitted by: ClinGen, Ambry Genetics
• Tourette syndrome

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020987.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANK3	NM_020987.5	MANE Select	c.1690-6_1690-4delTTT		splice_region intron	N/A	NP_066267.2
	ANK3	NM_001204404.2		c.1639-6_1639-4delTTT		splice_region intron	N/A	NP_001191333.1	Q12955-4
	ANK3	NM_001320874.2		c.1690-6_1690-4delTTT		splice_region intron	N/A	NP_001307803.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANK3	ENST00000280772.7	TSL:1 MANE Select	c.1690-6_1690-4delTTT		splice_region intron	N/A	ENSP00000280772.1	Q12955-3
	ANK3	ENST00000373827.6	TSL:1	c.1672-6_1672-4delTTT		splice_region intron	N/A	ENSP00000362933.2	Q12955-5
	ANK3	ENST00000503366.6	TSL:2	c.1639-6_1639-4delTTT		splice_region intron	N/A	ENSP00000425236.1	Q12955-4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 133088 Hom.: 0 Cov.: 28

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: 0.00000266 AC: 3 AN: 1127480 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 565256

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26170

American (AMR) AF: 0.00 AC: 0 AN: 32838

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21026

East Asian (EAS) AF: 0.00 AC: 0 AN: 33604

South Asian (SAS) AF: 0.00 AC: 0 AN: 67562

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4678

European-Non Finnish (NFE) AF: 0.00000350 AC: 3 AN: 856948

Other (OTH) AF: 0.00 AC: 0 AN: 47280

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 133088 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 63808

African (AFR) AF: 0.00 AC: 0 AN: 37066

American (AMR) AF: 0.00 AC: 0 AN: 13036

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3192

East Asian (EAS) AF: 0.00 AC: 0 AN: 4696

South Asian (SAS) AF: 0.00 AC: 0 AN: 4232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7022

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 60998

Other (OTH) AF: 0.00 AC: 0 AN: 1774

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs34796699; hg19: chr10-61956386;