16-4730261-G-A

Variant names:

• chr16-4730261-G-A
• rs859302
• NM_133450.4:c.-2-110C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

ANKS3 Gene-Disease associations (from GenCC):

• situs inversus

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• laterality defects, autosomal dominant

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000266994 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133450.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKS3	NM_133450.4	MANE Select	c.-2-110C>T		intron	N/A	NP_597707.1
	ANKS3	NM_001242929.2		c.-2-110C>T		intron	N/A	NP_001229858.1
	ANKS3	NM_001308089.2		c.-190-110C>T		intron	N/A	NP_001295018.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKS3	ENST00000304283.9	TSL:2 MANE Select	c.-2-110C>T		intron	N/A	ENSP00000304586.4
	ANKS3	ENST00000592077.5	TSL:1	n.-2-110C>T		intron	N/A	ENSP00000465203.1
	ANKS3	ENST00000585773.5	TSL:2	c.-49-3084C>T		intron	N/A	ENSP00000465294.1

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

African (AFR) AF: 0.504 AC: 10228 AN: 20284

American (AMR) AF: 0.507 AC: 5506 AN: 10868

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 8064 AN: 14546

East Asian (EAS) AF: 0.682 AC: 18565 AN: 27216

South Asian (SAS) AF: 0.509 AC: 17199 AN: 33788

European-Finnish (FIN) AF: 0.583 AC: 16418 AN: 28148

Middle Eastern (MID) AF: 0.608 AC: 1694 AN: 2788

European-Non Finnish (NFE) AF: 0.595 AC: 459240 AN: 771644

Other (OTH) AF: 0.575 AC: 23291 AN: 40478

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

African (AFR) AF: 0.495 AC: 20522 AN: 41474

American (AMR) AF: 0.509 AC: 7775 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 1884 AN: 3470

East Asian (EAS) AF: 0.667 AC: 3451 AN: 5174

South Asian (SAS) AF: 0.510 AC: 2462 AN: 4824

European-Finnish (FIN) AF: 0.569 AC: 6022 AN: 10582

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.597 AC: 40594 AN: 67976

Other (OTH) AF: 0.537 AC: 1135 AN: 2114

Alfa AF: 0.571 Hom.: 8786

Bravo AF: 0.552

Asia WGS AF: 0.536 AC: 1865 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.62
DANN	Benign	0.71
PhyloP100		-0.87
PromoterAI		0.0029	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs859302; hg19: chr16-4780262;