Genetic Variant ANKRD36:p.Ala228Ala (chr2-97124550-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001354587.1(ANKRD36):c.684G>A(p.Ala228Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00289 in 1,553,120 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 2 hom., cov: 30)

Exomes 𝑓: 0.0030 ( 10 hom. )

Consequence

ANKRD36
NM_001354587.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.70

Publications

1 publications found

Variant links:

Genes affected

ANKRD36 (HGNC:24079): (ankyrin repeat domain 36)

ANKRD36 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BP6

Variant 2-97124550-G-A is Benign according to our data. Variant chr2-97124550-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2651159.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.7 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354587.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD36	NM_001354587.1	MANE Select	c.684G>A	p.Ala228Ala	synonymous	Exon 5 of 76	NP_001341516.1	A6QL64-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKRD36	ENST00000420699.9	TSL:5 MANE Select	c.684G>A	p.Ala228Ala	synonymous	Exon 5 of 76	ENSP00000391950.4	A6QL64-1
ANKRD36	ENST00000461153.7	TSL:5	c.684G>A	p.Ala228Ala	synonymous	Exon 5 of 75	ENSP00000419530.3	A6QL64-1
ANKRD36	ENST00000652721.1		c.684G>A	p.Ala228Ala	synonymous	Exon 5 of 76	ENSP00000498611.1	A6QL64-1

Frequencies

GnomAD3 genomes

AF:

0.00186

AC:

282

AN:

151896

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000435

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000724

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.00425

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00297

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00186

AC:

306

AN:

164162

AF XY:

0.00177

show subpopulations

Gnomad AFR exome

AF:

0.000217

Gnomad AMR exome

AF:

0.000845

Gnomad ASJ exome

AF:

0.000115

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00392

Gnomad NFE exome

AF:

0.00303

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00301

AC:

4212

AN:

1401108

Hom.:

Cov.:

AF XY:

0.00284

AC XY:

1961

AN XY:

691230

show subpopulations

African (AFR)

AF:

0.000314

AC:

AN:

31808

American (AMR)

AF:

0.00101

AC:

AN:

35732

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25212

East Asian (EAS)

AF:

0.00

AC:

AN:

36146

South Asian (SAS)

AF:

0.000214

AC:

AN:

79268

European-Finnish (FIN)

AF:

0.00440

AC:

218

AN:

49554

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.00347

AC:

3750

AN:

1079512

Other (OTH)

AF:

0.00311

AC:

181

AN:

58174

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

235

470

706

941

1176

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

152

304

456

608

760

<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:

0.00185

AC:

281

AN:

152012

Hom.:

Cov.:

AF XY:

0.00167

AC XY:

124

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.000434

AC:

AN:

41518

American (AMR)

AF:

0.000723

AC:

AN:

15222

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000209

AC:

AN:

4790

European-Finnish (FIN)

AF:

0.00425

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00296

AC:

201

AN:

67934

Other (OTH)

AF:

0.00237

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00158

Hom.:

Bravo

AF:

0.00174

Asia WGS

AF:

0.000290

AC:

AN:

3462

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

4.6

(source)

DANN

Benign

0.22

PhyloP100

-2.7

Mutation Taster

=100/0

polymorphism

(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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over