22-37843963-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_138797.4(ANKRD54):​c.276G>T​(p.Arg92Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

ANKRD54
NM_138797.4 missense

Scores

4
2
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.366
Variant links:
Genes affected
ANKRD54 (HGNC:25185): (ankyrin repeat domain 54) Predicted to enable protein kinase regulator activity. Predicted to be involved in positive regulation of erythrocyte differentiation; regulation of intracellular signal transduction; and regulation of protein kinase activity. Predicted to act upstream of or within nucleocytoplasmic transport. Predicted to be located in midbody. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.26845297).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ANKRD54NM_138797.4 linkc.276G>T p.Arg92Ser missense_variant Exon 1 of 8 ENST00000215941.9 NP_620152.1 Q6NXT1-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ANKRD54ENST00000215941.9 linkc.276G>T p.Arg92Ser missense_variant Exon 1 of 8 1 NM_138797.4 ENSP00000215941.4 Q6NXT1-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1255608
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
617738
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
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
Mar 07, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.276G>T (p.R92S) alteration is located in exon 1 (coding exon 1) of the ANKRD54 gene. This alteration results from a G to T substitution at nucleotide position 276, causing the arginine (R) at amino acid position 92 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
Pathogenic
0.61
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.0
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.030
T;.;T
Eigen
Benign
-0.36
Eigen_PC
Benign
-0.25
FATHMM_MKL
Benign
0.72
D
LIST_S2
Benign
0.81
T;T;T
M_CAP
Pathogenic
0.48
D
MetaRNN
Benign
0.27
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.69
N;.;.
PrimateAI
Pathogenic
0.86
D
PROVEAN
Benign
-1.0
N;N;N
REVEL
Benign
0.25
Sift
Benign
0.056
T;D;T
Sift4G
Benign
0.30
T;T;.
Polyphen
0.44
B;.;.
Vest4
0.35
MutPred
0.39
Gain of helix (P = 0.0117);Gain of helix (P = 0.0117);Gain of helix (P = 0.0117);
MVP
0.73
MPC
0.71
ClinPred
0.77
D
GERP RS
1.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.35
gMVP
0.54

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: rs1346680789; hg19: chr22-38239970; API