chr10-60356289-G-A

Variant names:

• chr10-60356289-G-A
• rs4948410
• NM_020987.5:c.114+33136C>T

Variant summary

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

The NM_020987.5(ANK3):​c.114+33136C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 152,168 control chromosomes in the GnomAD database, including 40,810 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 0.73 (40810 hom., cov: 33)
• Consequence: ANK3 NM_020987.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800
• Publications: 5 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.892 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.114+33136C>T		intron	N/A	NP_066267.2
	ANK3	NM_001204404.2		c.64-76650C>T		intron	N/A	NP_001191333.1
	ANK3	NM_001320874.2		c.114+33136C>T		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.114+33136C>T		intron	N/A	ENSP00000280772.1
	ANK3	ENST00000373827.6	TSL:1	c.97-76650C>T		intron	N/A	ENSP00000362933.2
	ANK3	ENST00000503366.6	TSL:2	c.64-76650C>T		intron	N/A	ENSP00000425236.1

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110652 AN: 152050 Hom.: 40777 Cov.: 33

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.749

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.748

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.778

Gnomad OTH AF: 0.745

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

GnomAD4 genome AF: 0.728 AC: 110729 AN: 152168 Hom.: 40810 Cov.: 33 AF XY: 0.734 AC XY: 54619 AN XY: 74404

African (AFR) AF: 0.603 AC: 25029 AN: 41496

American (AMR) AF: 0.742 AC: 11336 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.791 AC: 2743 AN: 3468

East Asian (EAS) AF: 0.748 AC: 3869 AN: 5172

South Asian (SAS) AF: 0.915 AC: 4423 AN: 4834

European-Finnish (FIN) AF: 0.748 AC: 7919 AN: 10590

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.778 AC: 52910 AN: 68002

Other (OTH) AF: 0.746 AC: 1576 AN: 2114

Alfa AF: 0.770 Hom.: 26588

Bravo AF: 0.716

Asia WGS AF: 0.801 AC: 2785 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.23
PhyloP100		-0.080
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: rs4948410; hg19: chr10-62116047;