dbSNP rs2139814184: ANKRD9:p.Ala214Ser (chr14-102507250-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152326.4(ANKRD9):c.640G>T(p.Ala214Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000185 in 1,080,472 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict 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. A214T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000019 ( 0 hom. )

Consequence

ANKRD9
NM_152326.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.102

Publications

0 publications found

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]

ANKRD9 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15775236).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152326.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKRD9	NM_152326.4	MANE Select	c.640G>T	p.Ala214Ser	missense	Exon 4 of 4	NP_689539.1	Q96BM1
ANKRD9	NM_001348651.2		c.640G>T	p.Ala214Ser	missense	Exon 4 of 4	NP_001335580.1	Q96BM1
ANKRD9	NM_001348652.2		c.640G>T	p.Ala214Ser	missense	Exon 3 of 3	NP_001335581.1	Q96BM1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKRD9	ENST00000286918.9	TSL:1 MANE Select	c.640G>T	p.Ala214Ser	missense	Exon 4 of 4	ENSP00000286918.4	Q96BM1
ANKRD9	ENST00000559651.1	TSL:1	c.640G>T	p.Ala214Ser	missense	Exon 2 of 2	ENSP00000454100.1	Q96BM1
ANKRD9	ENST00000560748.5	TSL:2	c.640G>T	p.Ala214Ser	missense	Exon 3 of 3	ENSP00000453650.1	Q96BM1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000185

AC:

AN:

1080472

Hom.:

Cov.:

AF XY:

0.00000193

AC XY:

AN XY:

517858

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20898

American (AMR)

AF:

0.00

AC:

AN:

6822

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12354

East Asian (EAS)

AF:

0.0000476

AC:

AN:

21022

South Asian (SAS)

AF:

0.0000303

AC:

AN:

32964

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2806

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

918306

Other (OTH)

AF:

0.00

AC:

AN:

41892

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.078

BayesDel_noAF

Benign

-0.35

CADD

Benign

0.29

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.0089

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.33

M_CAP

Pathogenic

0.60

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.76

MutationAssessor

Benign

0.41

PhyloP100

-0.10

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.46

REVEL

Benign

0.14

Sift

Benign

0.048

Sift4G

Benign

0.10

Polyphen

0.010

Vest4

0.063

MutPred

0.24

Gain of glycosylation at A214 (P = 2e-04)

MVP

0.78

MPC

1.2

ClinPred

0.027

GERP RS

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Varity_R

0.042

gMVP

0.18

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over