10-60033762-A-G

Variant names:

• chr10-60033762-A-G
• rs11813307
• NM_020987.5:c.*20-3936T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020987.5(ANK3):​c.*20-3936T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 151,820 control chromosomes in the GnomAD database, including 14,854 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 0.43 (14854 hom., cov: 30)
• Consequence: ANK3 NM_020987.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.235
• Publications: 2 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: Labcorp Genetics (formerly Invitae), Orphanet, 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)

ENSG00000232682 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANK3	NM_020987.5	MANE Select	c.*20-3936T>C		intron	N/A	NP_066267.2
	ANK3	NM_001204404.2		c.*20-3936T>C		intron	N/A	NP_001191333.1
	ANK3	NM_001320874.2		c.*20-3936T>C		intron	N/A	NP_001307803.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANK3	ENST00000280772.7	TSL:1 MANE Select	c.*20-3936T>C		intron	N/A	ENSP00000280772.1
	ANK3	ENST00000373827.6	TSL:1	c.*20-3936T>C		intron	N/A	ENSP00000362933.2
	ANK3	ENST00000355288.6	TSL:1	c.*20-3936T>C		intron	N/A	ENSP00000347436.2

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65228 AN: 151702 Hom.: 14845 Cov.: 30

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.696

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.468

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.430 AC: 65258 AN: 151820 Hom.: 14854 Cov.: 30 AF XY: 0.422 AC XY: 31314 AN XY: 74192

African (AFR) AF: 0.331 AC: 13687 AN: 41394

American (AMR) AF: 0.368 AC: 5615 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 1875 AN: 3468

East Asian (EAS) AF: 0.212 AC: 1091 AN: 5146

South Asian (SAS) AF: 0.425 AC: 2044 AN: 4812

European-Finnish (FIN) AF: 0.368 AC: 3869 AN: 10514

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.520 AC: 35324 AN: 67930

Other (OTH) AF: 0.471 AC: 991 AN: 2104

Alfa AF: 0.470 Hom.: 11101

Bravo AF: 0.423

Asia WGS AF: 0.370 AC: 1286 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.73
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs11813307; hg19: chr10-61793520;