10-60042595-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020987.5(ANK3):c.*19+77T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.753 in 1,367,112 control chromosomes in the GnomAD database, including 389,797 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.72 (40129 hom., cov: 32)
  • Exomes 𝑓: 0.76 (349668 hom.)
• Consequence: ANK3 NM_020987.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.12

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 10-60042595-A-T is Benign according to our data. Variant chr10-60042595-A-T is described in ClinVar as [Benign]. Clinvar id is 1192392.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANK3	NM_020987.5	c.*19+77T>A		intron_variant		ENST00000280772.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANK3	ENST00000280772.7	c.*19+77T>A		intron_variant		1	NM_020987.5

Frequencies

GnomAD3 genomes AF: 0.723 AC: 109948 AN: 151970 Hom.: 40119 Cov.: 32

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.678

Gnomad ASJ AF: 0.787

Gnomad EAS AF: 0.819

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.772

Gnomad OTH AF: 0.742

GnomAD4 exome AF: 0.757 AC: 919278 AN: 1215024 Hom.: 349668 AF XY: 0.756 AC XY: 459760 AN XY: 608464

Gnomad4 AFR exome AF: 0.653

Gnomad4 AMR exome AF: 0.573

Gnomad4 ASJ exome AF: 0.788

Gnomad4 EAS exome AF: 0.783

Gnomad4 SAS exome AF: 0.713

Gnomad4 FIN exome AF: 0.687

Gnomad4 NFE exome AF: 0.772

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.723 AC: 110001 AN: 152088 Hom.: 40129 Cov.: 32 AF XY: 0.722 AC XY: 53704 AN XY: 74332

Gnomad4 AFR AF: 0.652

Gnomad4 AMR AF: 0.677

Gnomad4 ASJ AF: 0.787

Gnomad4 EAS AF: 0.819

Gnomad4 SAS AF: 0.723

Gnomad4 FIN AF: 0.684

Gnomad4 NFE AF: 0.772

Gnomad4 OTH AF: 0.743

Alfa AF: 0.658 Hom.: 1957

Bravo AF: 0.718

Asia WGS AF: 0.755 AC: 2626 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual disability-hypotonia-spasticity-sleep disorder syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.30
Dann	Benign	0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs2393604; hg19: chr10-61802353;