rs202079424

Variant names:

• chr10-60279040-T-C
• rs202079424
• NM_020987.5:c.315+10A>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS1

The NM_020987.5(ANK3):​c.315+10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000423 in 1,613,354 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00051 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00041 (0 hom.)
• Consequence: ANK3 NM_020987.5 intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: -1.25

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

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 10-60279040-T-C is Benign according to our data. Variant chr10-60279040-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 434180.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000506 (77/152304) while in subpopulation AMR AF = 0.000719 (11/15298). AF 95% confidence interval is 0.000403. There are 1 homozygotes in GnomAd4. There are 33 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANK3	NM_020987.5	c.315+10A>G		intron_variant	Intron 3 of 43	ENST00000280772.7	NP_066267.2
ANK3	NM_001204404.2	c.264+10A>G		intron_variant	Intron 3 of 43		NP_001191333.1
ANK3	NM_001320874.2	c.315+10A>G		intron_variant	Intron 3 of 42		NP_001307803.1
ANK3	NM_001204403.2	c.297+10A>G		intron_variant	Intron 4 of 43		NP_001191332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANK3	ENST00000280772.7	c.315+10A>G		intron_variant	Intron 3 of 43	1	NM_020987.5	ENSP00000280772.1

Frequencies

GnomAD3 genomes AF: 0.000506 AC: 77 AN: 152186 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000439 AC: 110 AN: 250628 AF XY: 0.000473

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00116

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000583

Gnomad OTH exome AF: 0.000328

GnomAD4 exome AF: 0.000415 AC: 606 AN: 1461050 Hom.: 0 Cov.: 30 AF XY: 0.000389 AC XY: 283 AN XY: 726874

Gnomad4 AFR exome AF: 0.0000299 AC: 1 AN: 33456

Gnomad4 AMR exome AF: 0.00123 AC: 55 AN: 44690

Gnomad4 ASJ exome AF: 0.0000766 AC: 2 AN: 26122

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39684

Gnomad4 SAS exome AF: 0.00 AC: 0 AN: 86246

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53340

Gnomad4 NFE exome AF: 0.000466 AC: 518 AN: 1111390

Gnomad4 Remaining exome AF: 0.000464 AC: 28 AN: 60358

GnomAD4 genome AF: 0.000506 AC: 77 AN: 152304 Hom.: 1 Cov.: 32 AF XY: 0.000443 AC XY: 33 AN XY: 74474

Gnomad4 AFR AF: 0.0000481 AC: 0.0000481093 AN: 0.0000481093

Gnomad4 AMR AF: 0.000719 AC: 0.000719048 AN: 0.000719048

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000500 AC: 0.000499809 AN: 0.000499809

Gnomad4 OTH AF: 0.000946 AC: 0.000946074 AN: 0.000946074

Alfa AF: 0.000553 Hom.: 0

Bravo AF: 0.000839

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not specified Uncertain:1

Jan 12, 2017

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.12
DANN	Benign	0.30
Mutation Taster		=100/0	polymorphism

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: rs202079424; hg19: chr10-62038798;