18-9254826-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015208.5(ANKRD12):ā€‹c.1559A>Gā€‹(p.Asn520Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000749 in 1,334,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 7.5e-7 ( 0 hom. )

Consequence

ANKRD12
NM_015208.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.370
Variant links:
Genes affected
ANKRD12 (HGNC:29135): (ankyrin repeat domain 12) This gene encodes a member of the ankyrin repeats-containing cofactor family. These proteins may inhibit the transcriptional activity of nuclear receptors through the recruitment of histone deacetylases. The encoded protein interacts with p160 coactivators and also represses transcription mediated by the coactivator alteration/deficiency in activation 3 (ADA3). Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.03458616).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ANKRD12NM_015208.5 linkuse as main transcriptc.1559A>G p.Asn520Ser missense_variant 9/13 ENST00000262126.9 NP_056023.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ANKRD12ENST00000262126.9 linkuse as main transcriptc.1559A>G p.Asn520Ser missense_variant 9/131 NM_015208.5 ENSP00000262126 P4Q6UB98-1
ANKRD12ENST00000400020.7 linkuse as main transcriptc.1490A>G p.Asn497Ser missense_variant 8/121 ENSP00000382897 A2Q6UB98-2
ANKRD12ENST00000359158.7 linkuse as main transcriptc.*673A>G 3_prime_UTR_variant, NMD_transcript_variant 4/42 ENSP00000352073

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.49e-7
AC:
1
AN:
1334962
Hom.:
0
Cov.:
33
AF XY:
0.00000153
AC XY:
1
AN XY:
654002
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:
0.0000160
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 31, 2023The c.1559A>G (p.N520S) alteration is located in exon 9 (coding exon 8) of the ANKRD12 gene. This alteration results from a A to G substitution at nucleotide position 1559, causing the asparagine (N) at amino acid position 520 to be replaced by a serine (S). 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
0.060
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
1.7
DANN
Benign
0.82
DEOGEN2
Benign
0.0072
T;.
Eigen
Benign
-0.82
Eigen_PC
Benign
-0.65
FATHMM_MKL
Benign
0.44
N
LIST_S2
Uncertain
0.87
D;D
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.035
T;T
MetaSVM
Benign
-0.77
T
MutationAssessor
Benign
0.20
N;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.37
T
PROVEAN
Benign
0.28
N;.
REVEL
Benign
0.21
Sift
Benign
0.38
T;.
Sift4G
Benign
0.98
T;T
Polyphen
0.0
B;B
Vest4
0.045
MutPred
0.12
Gain of phosphorylation at N520 (P = 0.0046);.;
MVP
0.47
ClinPred
0.13
T
GERP RS
0.80
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.011
gMVP
0.012

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: rs900435043; hg19: chr18-9254824; API