10-60055638-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_020987.5(ANK3):c.13065+20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000846 in 1,578,694 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0044 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00047 (7 hom.)
• Consequence: ANK3 NM_020987.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.05

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 10-60055638-C-T is Benign according to our data. Variant chr10-60055638-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 446050.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00439 (669/152278) while in subpopulation AFR AF= 0.0147 (611/41560). AF 95% confidence interval is 0.0137. There are 2 homozygotes in gnomad4. There are 303 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANK3	NM_020987.5	c.13065+20G>A		intron_variant		ENST00000280772.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANK3	ENST00000280772.7	c.13065+20G>A		intron_variant		1	NM_020987.5
	ENST00000619719.1	n.63-3696C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00440 AC: 670 AN: 152160 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.0148

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00383

GnomAD3 exomes AF: 0.00121 AC: 270 AN: 223888 Hom.: 2 AF XY: 0.000876 AC XY: 106 AN XY: 120954

Gnomad AFR exome AF: 0.0158

Gnomad AMR exome AF: 0.000496

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000400

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000573

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000468 AC: 667 AN: 1426416 Hom.: 7 Cov.: 32 AF XY: 0.000414 AC XY: 293 AN XY: 707448

Gnomad4 AFR exome AF: 0.0158

Gnomad4 AMR exome AF: 0.000695

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.0000623

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000474

Gnomad4 OTH exome AF: 0.00126

GnomAD4 genome AF: 0.00439 AC: 669 AN: 152278 Hom.: 2 Cov.: 33 AF XY: 0.00407 AC XY: 303 AN XY: 74458

Gnomad4 AFR AF: 0.0147

Gnomad4 AMR AF: 0.00255

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.00279 Hom.: 0

Bravo AF: 0.00541

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 07, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Aug 24, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.35
Dann	Benign	0.72

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: rs142778119; hg19: chr10-61815396;