Genetic Variant ANKRD22:p.Gln148Pro (chr10-88823335-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_144590.3(ANKRD22):c.443A>C(p.Gln148Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0443 in 1,613,796 control chromosomes in the GnomAD database, including 2,894 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.086 ( 1056 hom., cov: 30)

Exomes 𝑓: 0.040 ( 1838 hom. )

Consequence

ANKRD22
NM_144590.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.31

Publications

9 publications found

Variant links:

Genes affected

ANKRD22 (HGNC:28321): (ankyrin repeat domain 22)

ANKRD22 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016914606).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD22	NM_144590.3 link	c.443A>C	p.Gln148Pro	missense_variant	Exon 5 of 6	ENST00000371930.5	NP_653191.2	Q5VYY1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD22	ENST00000371930.5 link	c.443A>C	p.Gln148Pro	missense_variant	Exon 5 of 6	1	NM_144590.3	ENSP00000360998.4		Q5VYY1
ANKRD22	ENST00000476963.1 link	n.181A>C		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.0858

AC:

13050

AN:

152078

Hom.:

1055

Cov.:

show subpopulations

Gnomad AFR

AF:

0.215

Gnomad AMI

AF:

0.114

Gnomad AMR

AF:

0.0527

Gnomad ASJ

AF:

0.0553

Gnomad EAS

AF:

0.00405

Gnomad SAS

AF:

0.0271

Gnomad FIN

AF:

0.0194

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0372

Gnomad OTH

AF:

0.0741

GnomAD2 exomes

AF:

0.0444

AC:

11177

AN:

251472

AF XY:

0.0410

show subpopulations

Gnomad AFR exome

AF:

0.213

Gnomad AMR exome

AF:

0.0394

Gnomad ASJ exome

AF:

0.0568

Gnomad EAS exome

AF:

0.00343

Gnomad FIN exome

AF:

0.0191

Gnomad NFE exome

AF:

0.0371

Gnomad OTH exome

AF:

0.0495

GnomAD4 exome

AF:

0.0400

AC:

58406

AN:

1461600

Hom.:

1838

Cov.:

AF XY:

0.0392

AC XY:

28488

AN XY:

727122

show subpopulations

African (AFR)

AF:

0.217

AC:

7259

AN:

33454

American (AMR)

AF:

0.0425

AC:

1901

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0556

AC:

1454

AN:

26132

East Asian (EAS)

AF:

0.0111

AC:

442

AN:

39700

South Asian (SAS)

AF:

0.0252

AC:

2174

AN:

86256

European-Finnish (FIN)

AF:

0.0193

AC:

1033

AN:

53418

Middle Eastern (MID)

AF:

0.0864

AC:

498

AN:

5766

European-Non Finnish (NFE)

AF:

0.0364

AC:

40520

AN:

1111766

Other (OTH)

AF:

0.0518

AC:

3125

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

2735

5471

8206

10942

13677

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1600

3200

4800

6400

8000

<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:

0.0859

AC:

13073

AN:

152196

Hom.:

1056

Cov.:

AF XY:

0.0828

AC XY:

6163

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.215

AC:

8905

AN:

41488

American (AMR)

AF:

0.0526

AC:

805

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0553

AC:

192

AN:

3472

East Asian (EAS)

AF:

0.00406

AC:

AN:

5178

South Asian (SAS)

AF:

0.0269

AC:

130

AN:

4828

European-Finnish (FIN)

AF:

0.0194

AC:

206

AN:

10614

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0372

AC:

2528

AN:

67994

Other (OTH)

AF:

0.0733

AC:

155

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

542

1083

1625

2166

2708

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

264

396

528

660

<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:

0.0528

Hom.:

1623

Bravo

AF:

0.0934

TwinsUK

AF:

0.0453

AC:

168

ALSPAC

AF:

0.0397

AC:

153

ESP6500AA

AF:

0.192

AC:

844

ESP6500EA

AF:

0.0406

AC:

349

ExAC

AF:

0.0469

AC:

5688

Asia WGS

AF:

0.0300

AC:

105

AN:

3478

EpiCase

AF:

0.0416

EpiControl

AF:

0.0405

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0050

Eigen

Benign

-0.082

Eigen_PC

Benign

0.016

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.78

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.10

PhyloP100

2.3

PrimateAI

Benign

0.39

PROVEAN

Benign

-2.0

REVEL

Benign

0.055

Sift

Benign

0.18

Sift4G

Benign

0.32

Polyphen

0.75

Vest4

0.18

MPC

0.54

ClinPred

0.024

GERP RS

3.3

Varity_R

0.45

gMVP

0.66

Mutation Taster

=95/5

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over