dbSNP rs2296136: ANKRD16:p.Ala128Gly (chr10-5887999-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_019046.3(ANKRD16):c.383C>G(p.Ala128Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0402 in 1,614,122 control chromosomes in the GnomAD database, including 1,783 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 0.035 ( 165 hom., cov: 32)

Exomes 𝑓: 0.041 ( 1618 hom. )

Consequence

ANKRD16
NM_019046.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.65

Publications

17 publications found

Variant links:

Genes affected

ANKRD16 (HGNC:23471): (ankyrin repeat domain 16) Predicted to be involved in tRNA modification. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ANKRD16 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=0.0026624203).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD16	NM_019046.3 link	c.383C>G	p.Ala128Gly	missense_variant	Exon 2 of 8	ENST00000380094.10	NP_061919.1	Q6P6B7-1
ANKRD16	NM_001009941.3 link	c.383C>G	p.Ala128Gly	missense_variant	Exon 2 of 7		NP_001009941.1	Q6P6B7-1
ANKRD16	NM_001009943.3 link	c.383C>G	p.Ala128Gly	missense_variant	Exon 2 of 6		NP_001009943.1	Q6P6B7-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ANKRD16	ENST00000380094.10 link	c.383C>G	p.Ala128Gly	missense_variant	Exon 2 of 8	2	NM_019046.3	ENSP00000369436.4	Q6P6B7-1
ANKRD16	ENST00000380092.8 link	c.383C>G	p.Ala128Gly	missense_variant	Exon 2 of 7	1		ENSP00000369434.4	Q6P6B7-1
ANKRD16	ENST00000191063.8 link	c.383C>G	p.Ala128Gly	missense_variant	Exon 2 of 6	3		ENSP00000352361.6	Q6P6B7-2
ANKRD16	ENST00000492368.1 link	n.-29C>G		upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0346

AC:

5272

AN:

152176

Hom.:

164

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00794

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.0293

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.133

Gnomad SAS

AF:

0.0877

Gnomad FIN

AF:

0.0751

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0360

Gnomad OTH

AF:

0.0325

GnomAD2 exomes

AF:

0.0527

AC:

13264

AN:

251492

AF XY:

0.0538

show subpopulations

Gnomad AFR exome

AF:

0.00707

Gnomad AMR exome

AF:

0.0539

Gnomad ASJ exome

AF:

0.0118

Gnomad EAS exome

AF:

0.143

Gnomad FIN exome

AF:

0.0690

Gnomad NFE exome

AF:

0.0369

Gnomad OTH exome

AF:

0.0482

GnomAD4 exome

AF:

0.0408

AC:

59581

AN:

1461828

Hom.:

1618

Cov.:

AF XY:

0.0418

AC XY:

30375

AN XY:

727216

show subpopulations

African (AFR)

AF:

0.00597

AC:

200

AN:

33480

American (AMR)

AF:

0.0498

AC:

2228

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0129

AC:

337

AN:

26136

East Asian (EAS)

AF:

0.107

AC:

4262

AN:

39698

South Asian (SAS)

AF:

0.0819

AC:

7062

AN:

86254

European-Finnish (FIN)

AF:

0.0682

AC:

3643

AN:

53412

Middle Eastern (MID)

AF:

0.0160

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0353

AC:

39287

AN:

1111968

Other (OTH)

AF:

0.0409

AC:

2470

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

3430

6860

10291

13721

17151

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1582

3164

4746

6328

7910

<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:

0.0347

AC:

5280

AN:

152294

Hom.:

165

Cov.:

AF XY:

0.0380

AC XY:

2832

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.00791

AC:

329

AN:

41578

American (AMR)

AF:

0.0294

AC:

450

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00605

AC:

AN:

3472

East Asian (EAS)

AF:

0.134

AC:

691

AN:

5176

South Asian (SAS)

AF:

0.0871

AC:

420

AN:

4822

European-Finnish (FIN)

AF:

0.0751

AC:

797

AN:

10606

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0360

AC:

2449

AN:

68020

Other (OTH)

AF:

0.0365

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

238

476

715

953

1191

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

204

272

340

<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:

0.0315

Hom.:

Bravo

AF:

0.0296

TwinsUK

AF:

0.0359

AC:

133

ALSPAC

AF:

0.0355

AC:

137

ESP6500AA

AF:

0.00999

AC:

ESP6500EA

AF:

0.0349

AC:

300

ExAC

AF:

0.0529

AC:

6417

Asia WGS

AF:

0.130

AC:

449

AN:

3478

EpiCase

AF:

0.0303

EpiControl

AF:

0.0312

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.022

T;T;.

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.88

.;D;D

MetaRNN

Benign

0.0027

T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.7

M;M;M

PhyloP100

7.6

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-3.8

D;D;D

REVEL

Uncertain

0.33

Sift

Uncertain

0.011

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.28

MPC

0.75

ClinPred

0.021

GERP RS

2.9

Varity_R

0.51

gMVP

0.57

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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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