Genetic Variant ANKRD36:p.Lys5Glu (chr2-97113752-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001354587.1(ANKRD36):c.13A>G(p.Lys5Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 1,588,970 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 5 hom., cov: 31)

Exomes 𝑓: 0.0012 ( 29 hom. )

Consequence

ANKRD36
NM_001354587.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.52

Variant links:

Genes affected

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

ANKRD36 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008763403).

BP6

Variant 2-97113752-A-G is Benign according to our data. Variant chr2-97113752-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2651157.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD36	NM_001354587.1 link	c.13A>G	p.Lys5Glu	missense_variant	Exon 1 of 76	ENST00000420699.9	NP_001341516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ANKRD36	ENST00000420699.9 link	c.13A>G	p.Lys5Glu	missense_variant	Exon 1 of 76	5	NM_001354587.1	ENSP00000391950.4	A6QL64-1
ANKRD36	ENST00000452478.2 link	n.201A>G		non_coding_transcript_exon_variant	Exon 1 of 3	1
ANKRD36	ENST00000461153.7 link	c.13A>G	p.Lys5Glu	missense_variant	Exon 1 of 75	5		ENSP00000419530.3	A6QL64-1
ANKRD36	ENST00000652721.1 link	c.13A>G	p.Lys5Glu	missense_variant	Exon 1 of 76			ENSP00000498611.1	A6QL64-1

Frequencies

GnomAD3 genomes

AF:

0.00251

AC:

333

AN:

132414

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000595

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00344

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000601

Gnomad SAS

AF:

0.00108

Gnomad FIN

AF:

0.00150

Gnomad MID

AF:

0.0194

Gnomad NFE

AF:

0.00407

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00101

AC:

216

AN:

213990

Hom.:

AF XY:

0.00102

AC XY:

119

AN XY:

116420

show subpopulations

Gnomad AFR exome

AF:

0.000133

Gnomad AMR exome

AF:

0.00141

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000337

Gnomad FIN exome

AF:

0.000323

Gnomad NFE exome

AF:

0.00160

Gnomad OTH exome

AF:

0.00133

GnomAD4 exome

AF:

0.00120

AC:

1755

AN:

1456456

Hom.:

Cov.:

AF XY:

0.00126

AC XY:

912

AN XY:

724492

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.00184

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.0000256

Gnomad4 SAS exome

AF:

0.000709

Gnomad4 FIN exome

AF:

0.000772

Gnomad4 NFE exome

AF:

0.00125

Gnomad4 OTH exome

AF:

0.00221

GnomAD4 genome

AF:

0.00251

AC:

332

AN:

132514

Hom.:

Cov.:

AF XY:

0.00237

AC XY:

152

AN XY:

64054

show subpopulations

Gnomad4 AFR

AF:

0.000593

Gnomad4 AMR

AF:

0.00343

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000603

Gnomad4 SAS

AF:

0.000865

Gnomad4 FIN

AF:

0.00150

Gnomad4 NFE

AF:

0.00407

Gnomad4 OTH

AF:

0.00477

Alfa

AF:

0.00173

Hom.:

Bravo

AF:

0.00262

ExAC

AF:

0.000344

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ANKRD36: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.0060

DANN

Benign

0.12

DEOGEN2

Benign

0.0033

.;.;.;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.23

T;T;T;T

M_CAP

Benign

0.0017

MetaRNN

Benign

0.0088

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.69

.;.;.;N

PrimateAI

Uncertain

0.50

PROVEAN

Benign

0.67

.;N;.;N

REVEL

Benign

0.010

Sift

Benign

1.0

.;T;.;T

Sift4G

Benign

1.0

.;T;T;T

Polyphen

0.0

.;.;.;B

Vest4

0.038, 0.083, 0.059

MVP

0.076

ClinPred

0.0042

GERP RS

-0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.063

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over