3-15670427-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001349278.2(ANKRD28):​c.3095G>A​(p.Arg1032His) variant causes a missense change. The variant allele was found at a frequency of 0.0000279 in 1,613,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

ANKRD28
NM_001349278.2 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.10
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 Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.03515652).
BS2
High AC in GnomAd4 at 10 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ANKRD28NM_001349278.2 linkc.3095G>A p.Arg1032His missense_variant Exon 28 of 28 ENST00000683139.1 NP_001336207.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ANKRD28ENST00000683139.1 linkc.3095G>A p.Arg1032His missense_variant Exon 28 of 28 NM_001349278.2 ENSP00000508086.1 O15084-4

Frequencies

GnomAD3 genomes
AF:
0.0000658
AC:
10
AN:
152060
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000121
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:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000482
AC:
12
AN:
248990
Hom.:
0
AF XY:
0.0000370
AC XY:
5
AN XY:
135066
show subpopulations
Gnomad AFR exome
AF:
0.000387
Gnomad AMR exome
AF:
0.000145
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:
0.00000887
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000239
AC:
35
AN:
1461676
Hom.:
0
Cov.:
31
AF XY:
0.0000165
AC XY:
12
AN XY:
727122
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.000201
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000151
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000117
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000657
AC:
10
AN:
152178
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74392
show subpopulations
Gnomad4 AFR
AF:
0.000120
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:
0.0000735
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000450
Hom.:
0
Bravo
AF:
0.0000718
ESP6500AA
AF:
0.000255
AC:
1
ESP6500EA
AF:
0.000120
AC:
1
ExAC
AF:
0.0000662
AC:
8
EpiCase
AF:
0.000109
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 16, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.3005G>A (p.R1002H) alteration is located in exon 28 (coding exon 28) of the ANKRD28 gene. This alteration results from a G to A substitution at nucleotide position 3005, causing the arginine (R) at amino acid position 1002 to be replaced by a histidine (H). 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
Benign
0.061
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.012
.;T
Eigen
Benign
-0.26
Eigen_PC
Benign
0.039
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Uncertain
0.94
D;.
M_CAP
Benign
0.0020
T
MetaRNN
Benign
0.035
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.90
.;N
PrimateAI
Benign
0.30
T
PROVEAN
Benign
0.65
.;N
REVEL
Benign
0.11
Sift
Benign
0.53
.;T
Sift4G
Benign
0.23
T;T
Polyphen
0.0
.;B
Vest4
0.070
MVP
0.40
MPC
0.22
ClinPred
0.057
T
GERP RS
4.7
Varity_R
0.057
gMVP
0.25

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.

Other links and lift over

dbSNP: rs377170071; hg19: chr3-15711934; COSMIC: COSV67517470; API