10-60028485-T-A

Variant names:

• chr10-60028485-T-A
• rs8677
• NM_020987.5:c.*1361A>T

Variant summary

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

The NM_020987.5(ANK3):​c.*1361A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0726 in 152,744 control chromosomes in the GnomAD database, including 619 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 0.072 (618 hom., cov: 32)
  • Exomes 𝑓: 0.12 (1 hom.)
• Consequence: ANK3 NM_020987.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.98
• Publications: 6 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: Orphanet, Labcorp Genetics (formerly Invitae), 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=-0.41).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.107 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANK3	NM_020987.5	MANE Select	c.*1361A>T		3_prime_UTR	Exon 44 of 44	NP_066267.2
	ANK3	NM_001204404.2		c.*1361A>T		3_prime_UTR	Exon 44 of 44	NP_001191333.1	Q12955-4
	ANK3	NM_001320874.2		c.*1361A>T		3_prime_UTR	Exon 43 of 43	NP_001307803.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANK3	ENST00000280772.7	TSL:1 MANE Select	c.*1361A>T		3_prime_UTR	Exon 44 of 44	ENSP00000280772.1	Q12955-3
	ANK3	ENST00000373827.6	TSL:1	c.*1361A>T		3_prime_UTR	Exon 44 of 44	ENSP00000362933.2	Q12955-5
	ANK3	ENST00000503366.6	TSL:2	c.*1361A>T		3_prime_UTR	Exon 44 of 44	ENSP00000425236.1	Q12955-4

Frequencies

GnomAD3 genomes AF: 0.0725 AC: 11037 AN: 152194 Hom.: 619 Cov.: 32

Gnomad AFR AF: 0.0179

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0582

Gnomad ASJ AF: 0.0885

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0143

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.0666

GnomAD4 exome AF: 0.120 AC: 52 AN: 432 Hom.: 1 Cov.: 0 AF XY: 0.100 AC XY: 26 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: 0.122 AC: 52 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

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

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.0724 AC: 11030 AN: 152312 Hom.: 618 Cov.: 32 AF XY: 0.0713 AC XY: 5308 AN XY: 74476

African (AFR) AF: 0.0178 AC: 741 AN: 41578

American (AMR) AF: 0.0581 AC: 889 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0885 AC: 307 AN: 3470

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5194

South Asian (SAS) AF: 0.0141 AC: 68 AN: 4822

European-Finnish (FIN) AF: 0.130 AC: 1380 AN: 10610

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7450 AN: 68028

Other (OTH) AF: 0.0654 AC: 138 AN: 2110

Alfa AF: 0.0672 Hom.: 99

Bravo AF: 0.0634

Asia WGS AF: 0.0130 AC: 44 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	16
DANN	Benign	0.91
PhyloP100		3.0
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: rs8677; hg19: chr10-61788243;