Genetic Variant ANKRD36:p.His42Arg (chr2-97113864-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001354587.1(ANKRD36):c.125A>G(p.His42Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000552 in 1,607,124 control chromosomes in the GnomAD database, including 77 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00059 ( 6 hom., cov: 32)

Exomes 𝑓: 0.00055 ( 71 hom. )

Consequence

ANKRD36
NM_001354587.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.92

Publications

5 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008392215).

BP6

Variant 2-97113864-A-G is Benign according to our data. Variant chr2-97113864-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2651158.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 6 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.125A>G	p.His42Arg	missense	Exon 1 of 76	NP_001341516.1	A6QL64-1
	ANKRD36	NM_198555.4		c.125A>G	p.His42Arg	missense	Exon 1 of 3	NP_940957.3	A6QL64-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKRD36	ENST00000420699.9	TSL:5 MANE Select	c.125A>G	p.His42Arg	missense	Exon 1 of 76	ENSP00000391950.4	A6QL64-1
ANKRD36	ENST00000452478.2	TSL:1	n.313A>G		non_coding_transcript_exon	Exon 1 of 3
ANKRD36	ENST00000461153.7	TSL:5	c.125A>G	p.His42Arg	missense	Exon 1 of 75	ENSP00000419530.3	A6QL64-1

Frequencies

GnomAD3 genomes

AF:

0.000587

AC:

AN:

148304

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000643

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000202

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00707

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000977

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000300

Gnomad OTH

AF:

0.000987

GnomAD2 exomes

AF:

0.000305

AC:

AN:

248910

AF XY:

0.000303

show subpopulations

Gnomad AFR exome

AF:

0.000454

Gnomad AMR exome

AF:

0.000319

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000842

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000274

Gnomad OTH exome

AF:

0.000826

GnomAD4 exome

AF:

0.000548

AC:

800

AN:

1458712

Hom.:

Cov.:

AF XY:

0.000562

AC XY:

408

AN XY:

725682

show subpopulations

African (AFR)

AF:

0.000692

AC:

AN:

33232

American (AMR)

AF:

0.000471

AC:

AN:

44592

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26108

East Asian (EAS)

AF:

0.0134

AC:

517

AN:

38534

South Asian (SAS)

AF:

0.000128

AC:

AN:

85996

European-Finnish (FIN)

AF:

0.0000376

AC:

AN:

53220

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000175

AC:

194

AN:

1111016

Other (OTH)

AF:

0.000349

AC:

AN:

60250

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

130

163

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000586

AC:

AN:

148412

Hom.:

Cov.:

AF XY:

0.000663

AC XY:

AN XY:

72424

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000641

AC:

AN:

40576

American (AMR)

AF:

0.000202

AC:

AN:

14880

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3418

East Asian (EAS)

AF:

0.00708

AC:

AN:

4802

South Asian (SAS)

AF:

0.00

AC:

AN:

4706

European-Finnish (FIN)

AF:

0.0000977

AC:

AN:

10236

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000300

AC:

AN:

66572

Other (OTH)

AF:

0.000980

AC:

AN:

2040

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000000660425), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.398

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.000255

Hom.:

ExAC

AF:

0.000364

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000652

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

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.15

(source)

DANN

Benign

0.20

DEOGEN2

Benign

0.0012

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0099

LIST_S2

Benign

0.075

M_CAP

Benign

0.0020

MetaRNN

Benign

0.0084

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.010

PhyloP100

-1.9

PrimateAI

Uncertain

0.63

PROVEAN

Benign

0.040

REVEL

Benign

0.051

Sift

Benign

0.40

Sift4G

Benign

0.34

Polyphen

0.0010

Vest4

0.087

MutPred

0.55

Gain of MoRF binding (P = 0.0065)

MVP

0.20

ClinPred

0.0058

GERP RS

-1.9

PromoterAI

0.069

Neutral

(source)

Varity_R

0.024

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