rs142415903

Variant names:

• chr10-60181410-G-A
• rs142415903
• NM_020987.5:c.2103C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-60181410-G-A
• chr10-60181410-G-C

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_020987.5(ANK3):​c.2103C>T​(p.Leu701Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00347 in 1,614,160 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0030 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0035 (15 hom.)
• Consequence: ANK3 NM_020987.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.07
• Publications: 0 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)

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 10-60181410-G-A is Benign according to our data. Variant chr10-60181410-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 210148.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.07 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00295 (450/152308) while in subpopulation NFE AF = 0.00426 (290/68028). AF 95% confidence interval is 0.00386. There are 2 homozygotes in GnomAd4. There are 208 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR,Unknown,AD gene

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.2103C>T	p.Leu701Leu	synonymous	Exon 18 of 44	NP_066267.2
	ANK3	NM_001204404.2		c.2052C>T	p.Leu684Leu	synonymous	Exon 18 of 44	NP_001191333.1	Q12955-4
	ANK3	NM_001320874.2		c.2103C>T	p.Leu701Leu	synonymous	Exon 18 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.2103C>T	p.Leu701Leu	synonymous	Exon 18 of 44	ENSP00000280772.1	Q12955-3
	ANK3	ENST00000373827.6	TSL:1	c.2085C>T	p.Leu695Leu	synonymous	Exon 19 of 44	ENSP00000362933.2	Q12955-5
	ANK3	ENST00000503366.6	TSL:2	c.2052C>T	p.Leu684Leu	synonymous	Exon 18 of 44	ENSP00000425236.1	Q12955-4

Frequencies

GnomAD3 genomes AF: 0.00296 AC: 450 AN: 152190 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000675

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00269

Gnomad ASJ AF: 0.00691

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00547

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00426

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00298 AC: 748 AN: 251386 AF XY: 0.00283

Gnomad AFR exome AF: 0.000554

Gnomad AMR exome AF: 0.000983

Gnomad ASJ exome AF: 0.00556

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00550

Gnomad NFE exome AF: 0.00448

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00352 AC: 5149 AN: 1461852 Hom.: 15 Cov.: 31 AF XY: 0.00351 AC XY: 2551 AN XY: 727234

African (AFR) AF: 0.000418 AC: 14 AN: 33480

American (AMR) AF: 0.000961 AC: 43 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00566 AC: 148 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000209 AC: 18 AN: 86256

European-Finnish (FIN) AF: 0.00453 AC: 242 AN: 53420

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.00404 AC: 4493 AN: 1111974

Other (OTH) AF: 0.00311 AC: 188 AN: 60394

GnomAD4 genome AF: 0.00295 AC: 450 AN: 152308 Hom.: 2 Cov.: 32 AF XY: 0.00279 AC XY: 208 AN XY: 74478

African (AFR) AF: 0.000673 AC: 28 AN: 41578

American (AMR) AF: 0.00268 AC: 41 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00691 AC: 24 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00547 AC: 58 AN: 10606

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00426 AC: 290 AN: 68028

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00284 Hom.: 0

Bravo AF: 0.00263

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00496

EpiControl AF: 0.00480

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	2.8
DANN	Benign	0.79
PhyloP100		-2.1
Mutation Taster		=69/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
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: rs142415903; hg19: chr10-61941168;