11-67289512-C-T

Variant summary

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

The NM_207354.3(ANKRD13D):​c.52C>T​(p.Arg18Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000328 in 1,522,412 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: 0.0000015 ( 0 hom. )

Consequence

ANKRD13D
NM_207354.3 missense

Scores

2
4
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.285
Variant links:
Genes affected
ANKRD13D (HGNC:27880): (ankyrin repeat domain 13D) The protein encoded by this gene is a member of the ankyrin repeat domain (ANKRD) 13 family, which currently consists of four proteins containing ubiquitin-interacting motifs. These proteins are integral membrane proteins that bind specifically to Lys-63-linked ubiquitin chains on membrane-bound proteins, targeting those proteins for rapid internalization. [provided by RefSeq, Dec 2016]

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=0.3211942).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ANKRD13DNM_207354.3 linkuse as main transcriptc.52C>T p.Arg18Trp missense_variant 1/15 ENST00000511455.7 NP_997237.2
ANKRD13DNM_001347901.2 linkuse as main transcriptc.-347C>T 5_prime_UTR_variant 1/16 NP_001334830.1
ANKRD13DXM_047426873.1 linkuse as main transcriptc.-459C>T 5_prime_UTR_variant 1/15 XP_047282829.1
ANKRD13DXR_428913.3 linkuse as main transcriptn.210C>T non_coding_transcript_exon_variant 1/11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ANKRD13DENST00000511455.7 linkuse as main transcriptc.52C>T p.Arg18Trp missense_variant 1/151 NM_207354.3 ENSP00000427130 P1Q6ZTN6-3

Frequencies

GnomAD3 genomes
AF:
0.0000198
AC:
3
AN:
151518
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000725
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000146
AC:
2
AN:
1370788
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
676550
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:
0.0000255
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000198
AC:
3
AN:
151624
Hom.:
0
Cov.:
32
AF XY:
0.0000405
AC XY:
3
AN XY:
74064
show subpopulations
Gnomad4 AFR
AF:
0.0000723
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

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 GeneticsFeb 27, 2024The c.52C>T (p.R18W) alteration is located in exon 1 (coding exon 1) of the ANKRD13D gene. This alteration results from a C to T substitution at nucleotide position 52, causing the arginine (R) at amino acid position 18 to be replaced by a tryptophan (W). 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
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.49
CADD
Pathogenic
29
DANN
Uncertain
1.0
Eigen
Benign
0.11
Eigen_PC
Benign
-0.0056
FATHMM_MKL
Benign
0.72
D
LIST_S2
Uncertain
0.97
D
M_CAP
Pathogenic
0.94
D
MetaRNN
Benign
0.32
T
MetaSVM
Benign
-0.73
T
MutationTaster
Benign
0.65
D;D;D;D
PrimateAI
Pathogenic
0.92
D
PROVEAN
Benign
-2.1
N
REVEL
Benign
0.13
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.0040
D
Polyphen
1.0
D
Vest4
0.19
MutPred
0.49
Loss of disorder (P = 0.0138);
MVP
0.10
MPC
0.97
ClinPred
0.83
D
GERP RS
1.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1039402945; hg19: chr11-67056983; API