rs4948256

Variant names:

• chr10-60197154-C-A
• rs4948256
• NM_020987.5:c.1690-529G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-60197154-C-A
• chr10-60197154-C-G
• chr10-60197154-C-T

Variant summary

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

The NM_020987.5(ANK3):​c.1690-529G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,194 control chromosomes in the GnomAD database, including 3,277 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 0.19 (3277 hom., cov: 32)
• Consequence: ANK3 NM_020987.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.744
• Publications: 9 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.362 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.1690-529G>T		intron	N/A	NP_066267.2
	ANK3	NM_001204404.2		c.1639-529G>T		intron	N/A	NP_001191333.1
	ANK3	NM_001320874.2		c.1690-529G>T		intron	N/A	NP_001307803.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANK3	ENST00000280772.7	TSL:1 MANE Select	c.1690-529G>T		intron	N/A	ENSP00000280772.1
	ANK3	ENST00000373827.6	TSL:1	c.1672-529G>T		intron	N/A	ENSP00000362933.2
	ANK3	ENST00000503366.6	TSL:2	c.1639-529G>T		intron	N/A	ENSP00000425236.1

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28288 AN: 152076 Hom.: 3283 Cov.: 32

Gnomad AFR AF: 0.0585

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.186 AC: 28269 AN: 152194 Hom.: 3277 Cov.: 32 AF XY: 0.190 AC XY: 14105 AN XY: 74398

African (AFR) AF: 0.0584 AC: 2428 AN: 41542

American (AMR) AF: 0.198 AC: 3026 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 785 AN: 3472

East Asian (EAS) AF: 0.376 AC: 1941 AN: 5166

South Asian (SAS) AF: 0.292 AC: 1409 AN: 4826

European-Finnish (FIN) AF: 0.275 AC: 2912 AN: 10578

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.221 AC: 15005 AN: 68006

Other (OTH) AF: 0.203 AC: 429 AN: 2114

Alfa AF: 0.210 Hom.: 6566

Bravo AF: 0.176

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.7
DANN	Benign	0.67
PhyloP100		0.74
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4948256; hg19: chr10-61956912;