Variant 14-102507042-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_152326.4(ANKRD9):c.848T>C(p.Met283Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000028 in 1,427,824 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: 0.0000028 ( 0 hom. )

Consequence

ANKRD9
NM_152326.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.00

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.915

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ANKRD9	NM_152326.4 linkuse as main transcript	c.848T>C	p.Met283Thr	missense_variant	4/4	ENST00000286918.9	NP_689539.1
ANKRD9	NM_001348651.2 linkuse as main transcript	c.848T>C	p.Met283Thr	missense_variant	4/4		NP_001335580.1
ANKRD9	NM_001348652.2 linkuse as main transcript	c.848T>C	p.Met283Thr	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.848T>C	p.Met283Thr	missense_variant	4/4	1	NM_152326.4	ENSP00000286918	P1
ANKRD9	ENST00000559651.1 linkuse as main transcript	c.848T>C	p.Met283Thr	missense_variant	2/2	1		ENSP00000454100	P1
ANKRD9	ENST00000560748.5 linkuse as main transcript	c.848T>C	p.Met283Thr	missense_variant	3/3	2		ENSP00000453650	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000526

AC:

AN:

190056

Hom.:

AF XY:

0.00

AC XY:

AN XY:

106604

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000116

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000280

AC:

AN:

1427824

Hom.:

Cov.:

AF XY:

0.00000282

AC XY:

AN XY:

709606

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:

0.00000363

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000850

AC:

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 13, 2023

The c.848T>C (p.M283T) alteration is located in exon 4 (coding exon 1) of the ANKRD9 gene. This alteration results from a T to C substitution at nucleotide position 848, causing the methionine (M) at amino acid position 283 to be replaced by a threonine (T). 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

Pathogenic

0.80

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

T;T;T

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.40

.;.;T

M_CAP

Pathogenic

0.65

MetaRNN

Pathogenic

0.91

D;D;D

MetaSVM

Uncertain

0.60

MutationAssessor

Uncertain

2.4

M;M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.94

PROVEAN

Uncertain

-3.6

D;D;D

REVEL

Pathogenic

0.79

Sift

Uncertain

0.0030

D;D;D

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

0.96

D;D;D

Vest4

0.56

MutPred

0.81

Loss of helix (P = 0.0072);Loss of helix (P = 0.0072);Loss of helix (P = 0.0072);

MVP

0.98

MPC

2.4

ClinPred

0.93

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.57

gMVP

0.63

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