3-15676987-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001349278.2(ANKRD28):c.2860G>A(p.Ala954Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000177 in 1,612,360 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00082 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 2 hom. )

Consequence

ANKRD28
NM_001349278.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.01

Publications

1 publications found

Variant links:

Genes affected

ANKRD28 (HGNC:29024): (ankyrin repeat domain 28) Predicted to be located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ANKRD28 links:

BTD (HGNC:1122): (biotinidase) The protein encoded by this gene functions to recycle protein-bound biotin by cleaving biocytin (biotin-epsilon-lysine), a normal product of carboxylase degradation, resulting in regeneration of free biotin. The encoded protein has also been shown to have biotinyl transferase activity. Mutations in this gene are associated with biotinidase deficiency. Multiple transcript variants encoding different isoforms have been described. [provided by RefSeq, Aug 2013]

BTD Gene-Disease associations (from GenCC):

biotinidase deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Myriad Women’s Health, Labcorp Genetics (formerly Invitae), G2P, Orphanet, Ambry Genetics
Leigh syndrome
Inheritance: AR Classification: MODERATE Submitted by: ClinGen

BTD links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012588114).

BS2

High AC in GnomAd4 at 124 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349278.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKRD28	NM_001349278.2	MANE Select	c.2860G>A	p.Ala954Thr	missense	Exon 26 of 28	NP_001336207.1	O15084-4
ANKRD28	NM_001349277.2		c.2869G>A	p.Ala957Thr	missense	Exon 26 of 28	NP_001336206.1	O15084-1
ANKRD28	NM_015199.4		c.2770G>A	p.Ala924Thr	missense	Exon 26 of 28	NP_056014.2	O15084-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKRD28	ENST00000683139.1	MANE Select	c.2860G>A	p.Ala954Thr	missense	Exon 26 of 28	ENSP00000508086.1	O15084-4
ANKRD28	ENST00000399451.6	TSL:1	c.2770G>A	p.Ala924Thr	missense	Exon 26 of 28	ENSP00000382379.2	O15084-3
ANKRD28	ENST00000624145.3	TSL:2	c.2308G>A	p.Ala770Thr	missense	Exon 26 of 28	ENSP00000485421.1	O15084-2

Frequencies

GnomAD3 genomes

AF:

0.000812

AC:

123

AN:

151546

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00277

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000529

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000265

AC:

AN:

248860

AF XY:

0.000222

show subpopulations

Gnomad AFR exome

AF:

0.00297

Gnomad AMR exome

AF:

0.000348

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000887

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000111

AC:

162

AN:

1460696

Hom.:

Cov.:

AF XY:

0.000110

AC XY:

AN XY:

726668

show subpopulations

African (AFR)

AF:

0.00308

AC:

103

AN:

33436

American (AMR)

AF:

0.000336

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.0000505

AC:

AN:

39624

South Asian (SAS)

AF:

0.000209

AC:

AN:

86238

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53352

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.0000126

AC:

AN:

1111146

Other (OTH)

AF:

0.000149

AC:

AN:

60324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.000818

AC:

124

AN:

151664

Hom.:

Cov.:

AF XY:

0.000891

AC XY:

AN XY:

74042

show subpopulations

African (AFR)

AF:

0.00278

AC:

115

AN:

41348

American (AMR)

AF:

0.000528

AC:

AN:

15148

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4800

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10474

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67934

Other (OTH)

AF:

0.00

AC:

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

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:

0.000460

Hom.:

Bravo

AF:

0.00110

ESP6500AA

AF:

0.00424

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000265

AC:

Asia WGS

AF:

0.000578

AC:

AN:

3476

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.016

Eigen

Benign

-0.18

Eigen_PC

Benign

0.049

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.0070

MetaRNN

Benign

0.013

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

PhyloP100

2.0

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.52

REVEL

Benign

0.049

Sift

Benign

0.46

Sift4G

Benign

0.81

Polyphen

0.0010

Vest4

0.37

MVP

0.47

MPC

0.18

ClinPred

0.019

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.051

gMVP

0.52

Mutation Taster

=78/22

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