5-56111447-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024669.3(ANKRD55):​c.1301C>T​(p.Thr434Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000105 in 1,614,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

ANKRD55
NM_024669.3 missense

Scores

6
5
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.33
Variant links:
Genes affected
ANKRD55 (HGNC:25681): (ankyrin repeat domain 55)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.25117946).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ANKRD55NM_024669.3 linkuse as main transcriptc.1301C>T p.Thr434Met missense_variant 10/12 ENST00000341048.9
ANKRD55XM_047417710.1 linkuse as main transcriptc.815C>T p.Thr272Met missense_variant 6/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ANKRD55ENST00000341048.9 linkuse as main transcriptc.1301C>T p.Thr434Met missense_variant 10/122 NM_024669.3 P1Q3KP44-1
ANKRD55ENST00000434982.2 linkuse as main transcriptc.437C>T p.Thr146Met missense_variant 2/41 Q3KP44-2
ANKRD55ENST00000504958.6 linkuse as main transcriptc.1172C>T p.Thr391Met missense_variant 8/105

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152170
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251170
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135740
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000958
AC:
14
AN:
1461878
Hom.:
0
Cov.:
33
AF XY:
0.0000110
AC XY:
8
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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:
0.0000108
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152288
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74466
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.0000247
AC:
3

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 24, 2023The c.1301C>T (p.T434M) alteration is located in exon 10 (coding exon 9) of the ANKRD55 gene. This alteration results from a C to T substitution at nucleotide position 1301, causing the threonine (T) at amino acid position 434 to be replaced by a methionine (M). 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
0.13
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.020
CADD
Pathogenic
27
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.048
T;T;.
Eigen
Pathogenic
0.70
Eigen_PC
Pathogenic
0.73
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Uncertain
0.94
D;D;D
M_CAP
Benign
0.030
D
MetaRNN
Benign
0.25
T;T;T
MetaSVM
Benign
-0.47
T
MutationAssessor
Uncertain
2.4
M;.;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-1.5
N;N;D
REVEL
Benign
0.26
Sift
Pathogenic
0.0
D;D;D
Sift4G
Pathogenic
0.0
D;D;D
Vest4
0.23
MVP
0.74
MPC
0.81
ClinPred
0.92
D
GERP RS
5.6
Varity_R
0.36
gMVP
0.75

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: rs770473679; hg19: chr5-55407274; COSMIC: COSV100591580; COSMIC: COSV100591580; API