12-56244686-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_173595.4(ANKRD52):​c.2688G>A​(p.Met896Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ANKRD52
NM_173595.4 missense

Scores

4
8
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91
Variant links:
Genes affected
ANKRD52 (HGNC:26614): (ankyrin repeat domain 52)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.848

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ANKRD52NM_173595.4 linkc.2688G>A p.Met896Ile missense_variant Exon 24 of 28 ENST00000267116.8 NP_775866.2 Q8NB46B3KWN0
ANKRD52XM_017019183.2 linkc.2685G>A p.Met895Ile missense_variant Exon 23 of 27 XP_016874672.1
ANKRD52XM_011538197.3 linkc.2505G>A p.Met835Ile missense_variant Exon 23 of 27 XP_011536499.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ANKRD52ENST00000267116.8 linkc.2688G>A p.Met896Ile missense_variant Exon 24 of 28 1 NM_173595.4 ENSP00000267116.7 Q8NB46
ANKRD52ENST00000548241.1 linkn.42G>A non_coding_transcript_exon_variant Exon 1 of 6 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
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
Jan 18, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2688G>A (p.M896I) alteration is located in exon 24 (coding exon 24) of the ANKRD52 gene. This alteration results from a G to A substitution at nucleotide position 2688, causing the methionine (M) at amino acid position 896 to be replaced by an isoleucine (I). 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
0.96
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.0
CADD
Pathogenic
29
DANN
Uncertain
0.99
DEOGEN2
Benign
0.069
T
Eigen
Uncertain
0.36
Eigen_PC
Uncertain
0.38
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.91
D
M_CAP
Benign
0.019
T
MetaRNN
Pathogenic
0.85
D
MetaSVM
Benign
-0.77
T
MutationAssessor
Benign
1.6
L
PrimateAI
Uncertain
0.68
T
PROVEAN
Uncertain
-2.7
D
REVEL
Uncertain
0.29
Sift
Benign
0.16
T
Sift4G
Benign
0.081
T
Polyphen
0.88
P
Vest4
0.85
MutPred
0.65
Gain of catalytic residue at R892 (P = 0.0011);
MVP
0.73
MPC
1.8
ClinPred
0.96
D
GERP RS
4.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.35
gMVP
0.80

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-56638470; API