NM_020987.5:c.2185-4060G>A

Variant names:

• chr10-60177246-C-T
• rs12355908
• NM_020987.5:c.2185-4060G>A

Variant summary

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

The NM_020987.5(ANK3):​c.2185-4060G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,090 control chromosomes in the GnomAD database, including 3,391 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 0.19 (3391 hom., cov: 32)
• Consequence: ANK3 NM_020987.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.301

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANK3	NM_020987.5	c.2185-4060G>A		intron_variant	Intron 18 of 43	ENST00000280772.7	NP_066267.2
ANK3	NM_001204404.2	c.2134-4060G>A		intron_variant	Intron 18 of 43		NP_001191333.1
ANK3	NM_001320874.2	c.2185-4060G>A		intron_variant	Intron 18 of 42		NP_001307803.1
ANK3	NM_001204403.2	c.2167-4060G>A		intron_variant	Intron 19 of 43		NP_001191332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANK3	ENST00000280772.7	c.2185-4060G>A		intron_variant	Intron 18 of 43	1	NM_020987.5	ENSP00000280772.1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29636 AN: 151970 Hom.: 3390 Cov.: 32

Gnomad AFR AF: 0.0843

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.195 AC: 29645 AN: 152090 Hom.: 3391 Cov.: 32 AF XY: 0.194 AC XY: 14424 AN XY: 74366

Gnomad4 AFR AF: 0.0843

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.159

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.197

Alfa AF: 0.231 Hom.: 2565

Bravo AF: 0.190

Asia WGS AF: 0.168 AC: 583 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.4
DANN	Benign	0.68

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: rs12355908; hg19: chr10-61937004;