chr14-102507415-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_152326.4(ANKRD9):​c.475G>A​(p.Gly159Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000822 in 1,217,138 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 8.2e-7 ( 0 hom. )

Consequence

ANKRD9
NM_152326.4 missense

Scores

3
8
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.29
Variant links:
Genes affected
ANKRD9 (HGNC:20096): (ankyrin repeat domain 9) Enables ubiquitin ligase-substrate adaptor activity. Involved in cellular copper ion homeostasis; proteasome-mediated ubiquitin-dependent protein catabolic process; and protein ubiquitination. Located in cytoplasmic vesicle and cytosol. Part of Cul5-RING ubiquitin ligase complex. [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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.749

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ANKRD9NM_152326.4 linkc.475G>A p.Gly159Ser missense_variant Exon 4 of 4 ENST00000286918.9 NP_689539.1
ANKRD9NM_001348651.2 linkc.475G>A p.Gly159Ser missense_variant Exon 4 of 4 NP_001335580.1
ANKRD9NM_001348652.2 linkc.475G>A p.Gly159Ser missense_variant Exon 3 of 3 NP_001335581.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ANKRD9ENST00000286918.9 linkc.475G>A p.Gly159Ser missense_variant Exon 4 of 4 1 NM_152326.4 ENSP00000286918.4 Q96BM1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
8.22e-7
AC:
1
AN:
1217138
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
598768
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000618
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
Aug 05, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.475G>A (p.G159S) alteration is located in exon 4 (coding exon 1) of the ANKRD9 gene. This alteration results from a G to A substitution at nucleotide position 475, causing the glycine (G) at amino acid position 159 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
Benign
0.17
BayesDel_addAF
Benign
0.011
T
BayesDel_noAF
Benign
-0.22
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.18
T;T;T;.
Eigen
Uncertain
0.50
Eigen_PC
Uncertain
0.43
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.75
.;.;T;T
M_CAP
Pathogenic
0.62
D
MetaRNN
Pathogenic
0.75
D;D;D;D
MetaSVM
Uncertain
-0.23
T
MutationAssessor
Uncertain
2.5
M;M;M;.
PrimateAI
Pathogenic
0.92
D
PROVEAN
Uncertain
-3.6
D;D;D;D
REVEL
Uncertain
0.43
Sift
Benign
0.18
T;T;T;T
Sift4G
Benign
0.17
T;T;T;.
Polyphen
1.0
D;D;D;.
Vest4
0.26
MutPred
0.64
Gain of glycosylation at G159 (P = 0.0093);Gain of glycosylation at G159 (P = 0.0093);Gain of glycosylation at G159 (P = 0.0093);Gain of glycosylation at G159 (P = 0.0093);
MVP
0.87
MPC
2.5
ClinPred
0.99
D
GERP RS
3.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.35
gMVP
0.69

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: rs545545019; hg19: chr14-102973752; API