rs16915157

chr10-60586880-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000373827.6(ANK3):c.96+28306G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 152,108 control chromosomes in the GnomAD database, including 3,545 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 0.20 (3545 hom., cov: 32)
• Consequence: ANK3 ENST00000373827.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.457

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]

LOC124902430 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124902430	XR_007062150.1	n.3081-8085G>A		intron_variant, non_coding_transcript_variant
ANK3	NM_001204403.2	c.96+28306G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANK3	ENST00000373827.6	c.96+28306G>A		intron_variant		1
ANK3	ENST00000510382.1	n.101+28306G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30515 AN: 151990 Hom.: 3540 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.201 AC: 30548 AN: 152108 Hom.: 3545 Cov.: 32 AF XY: 0.210 AC XY: 15613 AN XY: 74324

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.374

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.186

Alfa AF: 0.211 Hom.: 3971

Bravo AF: 0.198

Asia WGS AF: 0.368 AC: 1275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	2.3
Dann	Benign	0.48

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs16915157; hg19: chr10-62346638;