rs859302

Positions:

• chr16-4730261-G-A
• chr16-4730261-G-C
• chr16-4730261-G-T

Variant summary

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

The NM_133450.4(ANKS3):​c.-2-110C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 1,101,860 control chromosomes in the GnomAD database, including 189,376 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 0.56 (23811 hom., cov: 33)
  • Exomes 𝑓: 0.59 (165565 hom.)
• Consequence: ANKS3 NM_133450.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.870

Genes affected

ANKS3 (HGNC:29422): (ankyrin repeat and sterile alpha motif domain containing 3) Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKS3	NM_133450.4	c.-2-110C>T		intron_variant		ENST00000304283.9	NP_597707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKS3	ENST00000304283.9	c.-2-110C>T		intron_variant		2	NM_133450.4	ENSP00000304586	P1

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84572 AN: 151980 Hom.: 23786 Cov.: 33

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.666

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.544

GnomAD4 exome AF: 0.590 AC: 560205 AN: 949760 Hom.: 165565 Cov.: 12 AF XY: 0.589 AC XY: 271996 AN XY: 461806

Gnomad4 AFR exome AF: 0.504

Gnomad4 AMR exome AF: 0.507

Gnomad4 ASJ exome AF: 0.554

Gnomad4 EAS exome AF: 0.682

Gnomad4 SAS exome AF: 0.509

Gnomad4 FIN exome AF: 0.583

Gnomad4 NFE exome AF: 0.595

Gnomad4 OTH exome AF: 0.575

GnomAD4 genome AF: 0.556 AC: 84630 AN: 152100 Hom.: 23811 Cov.: 33 AF XY: 0.554 AC XY: 41177 AN XY: 74346

Gnomad4 AFR AF: 0.495

Gnomad4 AMR AF: 0.509

Gnomad4 ASJ AF: 0.543

Gnomad4 EAS AF: 0.667

Gnomad4 SAS AF: 0.510

Gnomad4 FIN AF: 0.569

Gnomad4 NFE AF: 0.597

Gnomad4 OTH AF: 0.537

Alfa AF: 0.569 Hom.: 4649

Bravo AF: 0.552

Asia WGS AF: 0.536 AC: 1865 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.62
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs859302; hg19: chr16-4780262;