rs11599447

Variant names:

• chr10-60109301-T-C
• rs11599447
• NM_020987.5:c.2949-247A>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.2949-247A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0475 in 152,220 control chromosomes in the GnomAD database, including 208 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 0.048 (208 hom., cov: 32)
• Consequence: ANK3 NM_020987.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.139
• Publications: 4 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANK3	NM_020987.5	c.2949-247A>G		intron_variant	Intron 26 of 43	ENST00000280772.7	NP_066267.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANK3	ENST00000280772.7	c.2949-247A>G		intron_variant	Intron 26 of 43	1	NM_020987.5	ENSP00000280772.1

Frequencies

GnomAD3 genomes AF: 0.0475 AC: 7224 AN: 152102 Hom.: 208 Cov.: 32

Gnomad AFR AF: 0.0451

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0329

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.00600

Gnomad FIN AF: 0.0624

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0578

Gnomad OTH AF: 0.0392

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

GnomAD4 genome AF: 0.0475 AC: 7237 AN: 152220 Hom.: 208 Cov.: 32 AF XY: 0.0455 AC XY: 3389 AN XY: 74434

African (AFR) AF: 0.0453 AC: 1880 AN: 41526

American (AMR) AF: 0.0329 AC: 503 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0320 AC: 111 AN: 3470

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5178

South Asian (SAS) AF: 0.00601 AC: 29 AN: 4828

European-Finnish (FIN) AF: 0.0624 AC: 661 AN: 10600

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0578 AC: 3930 AN: 68000

Other (OTH) AF: 0.0388 AC: 82 AN: 2114

Alfa AF: 0.0524 Hom.: 467

Bravo AF: 0.0445

Asia WGS AF: 0.0130 AC: 46 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.9
DANN	Benign	0.67
PhyloP100		-0.14
PromoterAI		0.014	Neutral
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: rs11599447; hg19: chr10-61869059;