rs8677

Positions:

• chr10-60028485-T-A
• chr10-60028485-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000280772.7(ANK3):​c.*1361A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0726 in 152,744 control chromosomes in the GnomAD database, including 619 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 0.072 (618 hom., cov: 32)
  • Exomes 𝑓: 0.12 (1 hom.)
• Consequence: ANK3 ENST00000280772.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.98

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANK3	NM_020987.5	c.*1361A>T		3_prime_UTR_variant	44/44	ENST00000280772.7	NP_066267.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANK3	ENST00000280772.7	c.*1361A>T		3_prime_UTR_variant	44/44	1	NM_020987.5	ENSP00000280772
ANK3	ENST00000373827.6	c.*1361A>T		3_prime_UTR_variant	44/44	1		ENSP00000362933
ANK3	ENST00000503366.6	c.*1361A>T		3_prime_UTR_variant	44/44	2		ENSP00000425236

Frequencies

GnomAD3 genomes AF: 0.0725 AC: 11037 AN: 152194 Hom.: 619 Cov.: 32

Gnomad AFR AF: 0.0179

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0582

Gnomad ASJ AF: 0.0885

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0143

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.0666

GnomAD4 exome AF: 0.120 AC: 52 AN: 432 Hom.: 1 Cov.: 0 AF XY: 0.100 AC XY: 26 AN XY: 260

Gnomad4 FIN exome AF: 0.122

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0724 AC: 11030 AN: 152312 Hom.: 618 Cov.: 32 AF XY: 0.0713 AC XY: 5308 AN XY: 74476

Gnomad4 AFR AF: 0.0178

Gnomad4 AMR AF: 0.0581

Gnomad4 ASJ AF: 0.0885

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0141

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.0654

Alfa AF: 0.0672 Hom.: 99

Bravo AF: 0.0634

Asia WGS AF: 0.0130 AC: 44 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	16
DANN	Benign	0.91

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: rs8677; hg19: chr10-61788243;