rs553687185

Variant summary

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

The NM_182608.4(ANKRD33):​c.781C>G​(p.Pro261Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,451,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P261S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

ANKRD33
NM_182608.4 missense

Scores

1
3
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.24
Variant links:
Genes affected
ANKRD33 (HGNC:13788): (ankyrin repeat domain 33) Predicted to be involved in negative regulation of transcription by RNA polymerase II and negative regulation of transcription regulatory region DNA binding activity. Predicted to act upstream of or within skeletal muscle cell differentiation. Predicted to be located in cytosol 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=0.3610715).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ANKRD33NM_182608.4 linkc.781C>G p.Pro261Ala missense_variant Exon 5 of 5 ENST00000301190.11 NP_872414.3 Q7Z3H0-2Q0VAA8Q5K617

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ANKRD33ENST00000301190.11 linkc.781C>G p.Pro261Ala missense_variant Exon 5 of 5 2 NM_182608.4 ENSP00000301190.6 Q7Z3H0-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000138
AC:
2
AN:
1451616
Hom.:
0
Cov.:
96
AF XY:
0.00
AC XY:
0
AN XY:
722640
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
23
DANN
Benign
0.88
Eigen
Uncertain
0.31
Eigen_PC
Uncertain
0.26
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.74
T;T
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.36
T;T
MetaSVM
Benign
-0.98
T
PrimateAI
Benign
0.44
T
PROVEAN
Pathogenic
-5.0
D;D
REVEL
Benign
0.14
Sift
Benign
0.64
T;T
Sift4G
Benign
0.067
T;T
Vest4
0.42
MutPred
0.46
.;Gain of catalytic residue at P139 (P = 0.0433);
MVP
0.72
MPC
0.49
ClinPred
0.89
D
GERP RS
4.7
Varity_R
0.23
gMVP
0.58

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-52284511; API