10-60347124-T-C

Variant names:

• chr10-60347124-T-C
• rs7084499
• NM_020987.5:c.114+42301A>G

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+42301A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.697 in 148,868 control chromosomes in the GnomAD database, including 37,470 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 0.70 (37470 hom., cov: 24)
• Consequence: ANK3 NM_020987.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.197
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANK3	NM_020987.5	c.114+42301A>G		intron_variant	Intron 1 of 43	ENST00000280772.7	NP_066267.2
ANK3	NM_001204404.2	c.64-67485A>G		intron_variant	Intron 1 of 43		NP_001191333.1
ANK3	NM_001320874.2	c.114+42301A>G		intron_variant	Intron 1 of 42		NP_001307803.1
ANK3	NM_001204403.2	c.97-67485A>G		intron_variant	Intron 2 of 43		NP_001191332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANK3	ENST00000280772.7	c.114+42301A>G		intron_variant	Intron 1 of 43	1	NM_020987.5	ENSP00000280772.1

Frequencies

GnomAD3 genomes AF: 0.697 AC: 103687 AN: 148750 Hom.: 37446 Cov.: 24

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.756

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.749

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.746

Gnomad MID AF: 0.806

Gnomad NFE AF: 0.777

Gnomad OTH AF: 0.725

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

GnomAD4 genome AF: 0.697 AC: 103755 AN: 148868 Hom.: 37470 Cov.: 24 AF XY: 0.704 AC XY: 50898 AN XY: 72342

African (AFR) AF: 0.496 AC: 19975 AN: 40304

American (AMR) AF: 0.730 AC: 10856 AN: 14864

Ashkenazi Jewish (ASJ) AF: 0.791 AC: 2727 AN: 3448

East Asian (EAS) AF: 0.748 AC: 3765 AN: 5034

South Asian (SAS) AF: 0.915 AC: 4219 AN: 4612

European-Finnish (FIN) AF: 0.746 AC: 7418 AN: 9948

Middle Eastern (MID) AF: 0.799 AC: 230 AN: 288

European-Non Finnish (NFE) AF: 0.777 AC: 52383 AN: 67400

Other (OTH) AF: 0.726 AC: 1496 AN: 2062

Alfa AF: 0.712 Hom.: 9898

Bravo AF: 0.682

Asia WGS AF: 0.797 AC: 2769 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.1
DANN	Benign	0.87
PhyloP100		-0.20
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: rs7084499; hg19: chr10-62106882;