Genetic Variant ANKS3:c.-2-110C>T (chr16-4730261-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.870

Publications

7 publications found

Variant links:

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

ANKS3 links:

ENSG00000266994 (HGNC:):

ENSG00000266994 links:

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ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ANKS3	NM_133450.4	MANE Select	c.-2-110C>T	intron	N/A	NP_597707.1	Q6ZW76-1
ANKS3	NM_001242929.2		c.-2-110C>T	intron	N/A	NP_001229858.1	F6WF08
ANKS3	NM_001308089.2		c.-190-110C>T	intron	N/A	NP_001295018.1	D3DUE4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ANKS3	ENST00000304283.9	TSL:2 MANE Select	c.-2-110C>T	intron	N/A	ENSP00000304586.4	Q6ZW76-1
ANKS3	ENST00000592077.5	TSL:1	n.-2-110C>T	intron	N/A	ENSP00000465203.1	K7EPP4
ANKS3	ENST00000875662.1		c.-2-110C>T	intron	N/A	ENSP00000545721.1

Frequencies

GnomAD3 genomes

AF:

0.556

AC:

84572

AN:

151980

Hom.:

23786

Cov.:

show subpopulations

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.:

AF XY:

0.589

AC XY:

271996

AN XY:

461806

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

11037

22074

33111

44148

55185

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13272

26544

39816

53088

66360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.556

AC:

84630

AN:

152100

Hom.:

23811

Cov.:

AF XY:

0.554

AC XY:

41177

AN XY:

74346

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1969

3937

5906

7874

9843

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

734

1468

2202

2936

3670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.71

PhyloP100

-0.87

PromoterAI

0.0029

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over