Variant 14-102507226-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152326.4(ANKRD9):c.664G>T(p.Gly222Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000036 in 1,112,604 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

ANKRD9
NM_152326.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.29

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]

ANKRD9 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ANKRD9	NM_152326.4 linkuse as main transcript	c.664G>T	p.Gly222Trp	missense_variant	4/4	ENST00000286918.9	NP_689539.1
ANKRD9	NM_001348651.2 linkuse as main transcript	c.664G>T	p.Gly222Trp	missense_variant	4/4		NP_001335580.1
ANKRD9	NM_001348652.2 linkuse as main transcript	c.664G>T	p.Gly222Trp	missense_variant	3/3		NP_001335581.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ANKRD9	ENST00000286918.9 linkuse as main transcript	c.664G>T	p.Gly222Trp	missense_variant	4/4	1	NM_152326.4	ENSP00000286918	P1
ANKRD9	ENST00000559651.1 linkuse as main transcript	c.664G>T	p.Gly222Trp	missense_variant	2/2	1		ENSP00000454100	P1
ANKRD9	ENST00000560748.5 linkuse as main transcript	c.664G>T	p.Gly222Trp	missense_variant	3/3	2		ENSP00000453650	P1
ANKRD9	ENST00000559404.5 linkuse as main transcript	c.664G>T	p.Gly222Trp	missense_variant	3/3	2		ENSP00000453417

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000360

AC:

AN:

1112604

Hom.:

Cov.:

AF XY:

0.00000187

AC XY:

AN XY:

534666

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:

0.0000276

Gnomad4 FIN exome

AF:

0.0000401

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000455

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

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 submitter

clinical testing

Ambry Genetics

Jun 07, 2023

The c.664G>T (p.G222W) alteration is located in exon 4 (coding exon 1) of the ANKRD9 gene. This alteration results from a G to T substitution at nucleotide position 664, causing the glycine (G) at amino acid position 222 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

AlphaMissense

Benign

0.19

BayesDel_addAF

Uncertain

0.060

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.025

T;T;T;.

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.52

.;.;T;T

M_CAP

Pathogenic

0.96

MetaRNN

Uncertain

0.52

D;D;D;D

MetaSVM

Benign

-0.32

MutationAssessor

Benign

1.4

L;L;L;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-1.9

N;N;N;N

REVEL

Uncertain

0.36

Sift

Benign

0.18

T;T;T;D

Sift4G

Uncertain

0.038

D;D;D;.

Polyphen

0.98

D;D;D;.

Vest4

0.33

MutPred

0.28

Loss of helix (P = 0.0093);Loss of helix (P = 0.0093);Loss of helix (P = 0.0093);Loss of helix (P = 0.0093);

MVP

0.93

MPC

2.4

ClinPred

0.48

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.068

gMVP

0.26

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over