rs16915157

Variant names:

• chr10-60586880-C-T
• rs16915157
• ENST00000373827.6:c.96+28306G>A

Variant summary

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

The ENST00000373827.6(ANK3):​c.96+28306G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 152,108 control chromosomes in the GnomAD database, including 3,545 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 0.20 (3545 hom., cov: 32)
• Consequence: ANK3 ENST00000373827.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.457
• Publications: 13 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)

LOC124902430 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANK3	NM_001204403.2	c.96+28306G>A		intron_variant	Intron 2 of 43		NP_001191332.1
LOC124902430	XR_007062150.1	n.3081-8085G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANK3	ENST00000373827.6	c.96+28306G>A		intron_variant	Intron 2 of 43	1		ENSP00000362933.2
ANK3	ENST00000510382.1	n.101+28306G>A		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30515 AN: 151990 Hom.: 3540 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.201 AC: 30548 AN: 152108 Hom.: 3545 Cov.: 32 AF XY: 0.210 AC XY: 15613 AN XY: 74324

African (AFR) AF: 0.114 AC: 4721 AN: 41522

American (AMR) AF: 0.292 AC: 4467 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 691 AN: 3472

East Asian (EAS) AF: 0.374 AC: 1927 AN: 5154

South Asian (SAS) AF: 0.368 AC: 1770 AN: 4816

European-Finnish (FIN) AF: 0.272 AC: 2872 AN: 10560

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13497 AN: 67992

Other (OTH) AF: 0.186 AC: 392 AN: 2112

Alfa AF: 0.207 Hom.: 7384

Bravo AF: 0.198

Asia WGS AF: 0.368 AC: 1275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.3
DANN	Benign	0.48
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs16915157; hg19: chr10-62346638;