chr10-60080409-C-T

Variant names:

• chr10-60080409-C-T
• rs7917800
• NM_020987.5:c.4432+128G>A

Variant summary

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

The NM_020987.5(ANK3):​c.4432+128G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 769,518 control chromosomes in the GnomAD database, including 4,960 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 0.13 (1572 hom., cov: 32)
  • Exomes 𝑓: 0.094 (3388 hom.)
• Consequence: ANK3 NM_020987.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.142
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.217 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.4432+128G>A		intron	N/A	NP_066267.2
	ANK3	NM_001204404.2		c.4408+128G>A		intron	N/A	NP_001191333.1	Q12955-4
	ANK3	NM_001320874.2		c.4405+128G>A		intron	N/A	NP_001307803.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANK3	ENST00000280772.7	TSL:1 MANE Select	c.4432+128G>A		intron	N/A	ENSP00000280772.1	Q12955-3
	ANK3	ENST00000373827.6	TSL:1	c.4387+128G>A		intron	N/A	ENSP00000362933.2	Q12955-5
	ANK3	ENST00000355288.6	TSL:1	c.1807+128G>A		intron	N/A	ENSP00000347436.2	Q12955-6

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19636 AN: 152044 Hom.: 1572 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.0911

Gnomad ASJ AF: 0.0576

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0178

Gnomad FIN AF: 0.0770

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.113

GnomAD4 exome AF: 0.0943 AC: 58246 AN: 617358 Hom.: 3388 AF XY: 0.0901 AC XY: 29364 AN XY: 325900

African (AFR) AF: 0.218 AC: 3255 AN: 14928

American (AMR) AF: 0.0687 AC: 1634 AN: 23800

Ashkenazi Jewish (ASJ) AF: 0.0653 AC: 1216 AN: 18630

East Asian (EAS) AF: 0.000458 AC: 14 AN: 30554

South Asian (SAS) AF: 0.0202 AC: 1111 AN: 54888

European-Finnish (FIN) AF: 0.0861 AC: 3384 AN: 39300

Middle Eastern (MID) AF: 0.0863 AC: 331 AN: 3834

European-Non Finnish (NFE) AF: 0.111 AC: 44168 AN: 399668

Other (OTH) AF: 0.0987 AC: 3133 AN: 31756

GnomAD4 genome AF: 0.129 AC: 19655 AN: 152160 Hom.: 1572 Cov.: 32 AF XY: 0.123 AC XY: 9160 AN XY: 74388

African (AFR) AF: 0.221 AC: 9162 AN: 41498

American (AMR) AF: 0.0910 AC: 1391 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0576 AC: 200 AN: 3470

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5184

South Asian (SAS) AF: 0.0172 AC: 83 AN: 4816

European-Finnish (FIN) AF: 0.0770 AC: 816 AN: 10600

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7670 AN: 67990

Other (OTH) AF: 0.112 AC: 237 AN: 2116

Alfa AF: 0.119 Hom.: 1572

Bravo AF: 0.135

Asia WGS AF: 0.0280 AC: 97 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.53
PhyloP100		-0.14
PromoterAI		-0.011	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: rs7917800; hg19: chr10-61840167; COSMIC: COSV55065712; COSMIC: COSV55065712;