3-15679314-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001349278.2(ANKRD28):​c.2548G>A​(p.Asp850Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,613,794 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

ANKRD28
NM_001349278.2 missense

Scores

6
5
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.84
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAdExome4 at 23 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ANKRD28NM_001349278.2 linkc.2548G>A p.Asp850Asn missense_variant Exon 23 of 28 ENST00000683139.1 NP_001336207.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ANKRD28ENST00000683139.1 linkc.2548G>A p.Asp850Asn missense_variant Exon 23 of 28 NM_001349278.2 ENSP00000508086.1 O15084-4

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152142
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000402
AC:
1
AN:
248876
Hom.:
0
AF XY:
0.00000741
AC XY:
1
AN XY:
134994
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000888
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000157
AC:
23
AN:
1461652
Hom.:
0
Cov.:
31
AF XY:
0.0000124
AC XY:
9
AN XY:
727116
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000207
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152142
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74326
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 06, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2458G>A (p.D820N) alteration is located in exon 23 (coding exon 23) of the ANKRD28 gene. This alteration results from a G to A substitution at nucleotide position 2458, causing the aspartic acid (D) at amino acid position 820 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.94
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.48
CADD
Pathogenic
29
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.16
.;T
Eigen
Pathogenic
0.82
Eigen_PC
Pathogenic
0.84
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.96
D;.
M_CAP
Benign
0.028
D
MetaRNN
Uncertain
0.74
D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Pathogenic
2.9
.;M
PrimateAI
Uncertain
0.71
T
PROVEAN
Uncertain
-3.7
.;D
REVEL
Uncertain
0.30
Sift
Benign
0.059
.;T
Sift4G
Benign
0.076
T;T
Polyphen
1.0
.;D
Vest4
0.69
MutPred
0.43
.;Loss of ubiquitination at K822 (P = 0.0699);
MVP
0.71
MPC
0.71
ClinPred
0.99
D
GERP RS
6.1
Varity_R
0.35
gMVP
0.54

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs1302708063; hg19: chr3-15720821; API