22-37843925-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_138797.4(ANKRD54):​c.314G>T​(p.Gly105Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000167 in 1,196,236 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000017 ( 0 hom. )

Consequence

ANKRD54
NM_138797.4 missense

Scores

4
11
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.01
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ANKRD54NM_138797.4 linkc.314G>T p.Gly105Val 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.314G>T p.Gly105Val missense_variant Exon 1 of 8 1 NM_138797.4 ENSP00000215941.4 Q6NXT1-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000167
AC:
2
AN:
1196236
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
584108
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000147
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

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 30, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.314G>T (p.G105V) 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 314, causing the glycine (G) at amino acid position 105 to be replaced by a valine (V). 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
Uncertain
0.46
BayesDel_addAF
Pathogenic
0.44
D
BayesDel_noAF
Pathogenic
0.40
CADD
Pathogenic
31
DANN
Uncertain
1.0
DEOGEN2
Benign
0.040
T;.;T
Eigen
Uncertain
0.59
Eigen_PC
Uncertain
0.62
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.85
D;T;D
M_CAP
Pathogenic
0.77
D
MetaRNN
Uncertain
0.65
D;D;D
MetaSVM
Uncertain
-0.13
T
MutationAssessor
Uncertain
2.8
M;.;.
PrimateAI
Pathogenic
0.83
D
PROVEAN
Uncertain
-2.4
N;D;N
REVEL
Uncertain
0.36
Sift
Uncertain
0.017
D;D;D
Sift4G
Benign
0.095
T;D;.
Polyphen
1.0
D;.;.
Vest4
0.79
MutPred
0.23
Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);
MVP
0.83
MPC
1.6
ClinPred
0.86
D
GERP RS
5.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.64
gMVP
0.63

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.12
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: rs1212997697; hg19: chr22-38239932; API