rs1049862

Variant names:

• chr10-60029514-G-A
• rs1049862
• NM_020987.5:c.*332C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-60029514-G-A
• chr10-60029514-G-C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_020987.5(ANK3):​c.*332C>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.361 in 152,434 control chromosomes in the GnomAD database, including 12,436 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 0.36 (12404 hom., cov: 31)
  • Exomes 𝑓: 0.36 (32 hom.)
• Consequence: ANK3 NM_020987.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.08
• Publications: 11 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.509 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.*332C>T		3_prime_UTR	Exon 44 of 44	NP_066267.2
	ANK3	NM_001204404.2		c.*332C>T		3_prime_UTR	Exon 44 of 44	NP_001191333.1
	ANK3	NM_001320874.2		c.*332C>T		3_prime_UTR	Exon 43 of 43	NP_001307803.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANK3	ENST00000280772.7	TSL:1 MANE Select	c.*332C>T		3_prime_UTR	Exon 44 of 44	ENSP00000280772.1
	ANK3	ENST00000373827.6	TSL:1	c.*332C>T		3_prime_UTR	Exon 44 of 44	ENSP00000362933.2
	ANK3	ENST00000503366.6	TSL:2	c.*332C>T		3_prime_UTR	Exon 44 of 44	ENSP00000425236.1

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54849 AN: 151884 Hom.: 12399 Cov.: 31

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.413

GnomAD4 exome AF: 0.361 AC: 156 AN: 432 Hom.: 32 Cov.: 0 AF XY: 0.377 AC XY: 98 AN XY: 260

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.362 AC: 154 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.361 AC: 54862 AN: 152002 Hom.: 12404 Cov.: 31 AF XY: 0.356 AC XY: 26428 AN XY: 74274

African (AFR) AF: 0.108 AC: 4460 AN: 41478

American (AMR) AF: 0.343 AC: 5239 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 1896 AN: 3472

East Asian (EAS) AF: 0.192 AC: 993 AN: 5174

South Asian (SAS) AF: 0.420 AC: 2020 AN: 4806

European-Finnish (FIN) AF: 0.361 AC: 3809 AN: 10540

Middle Eastern (MID) AF: 0.401 AC: 117 AN: 292

European-Non Finnish (NFE) AF: 0.513 AC: 34860 AN: 67950

Other (OTH) AF: 0.418 AC: 882 AN: 2112

Alfa AF: 0.386 Hom.: 4896

Bravo AF: 0.347

Asia WGS AF: 0.354 AC: 1232 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	17
DANN	Benign	0.80
PhyloP100		6.1
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: rs1049862; hg19: chr10-61789272;