NM_152326.4:c.544G>A

Variant names:

• chr14-102507346-C-T
• rs1396147502
• NM_152326.4:c.544G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_152326.4(ANKRD9):​c.544G>A​(p.Gly182Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000302 in 1,323,452 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: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: ANKRD9 NM_152326.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.11
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.911

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD9	NM_152326.4	MANE Select	c.544G>A	p.Gly182Ser	missense	Exon 4 of 4	NP_689539.1	Q96BM1
	ANKRD9	NM_001348651.2		c.544G>A	p.Gly182Ser	missense	Exon 4 of 4	NP_001335580.1	Q96BM1
	ANKRD9	NM_001348652.2		c.544G>A	p.Gly182Ser	missense	Exon 3 of 3	NP_001335581.1	Q96BM1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD9	ENST00000286918.9	TSL:1 MANE Select	c.544G>A	p.Gly182Ser	missense	Exon 4 of 4	ENSP00000286918.4	Q96BM1
	ANKRD9	ENST00000559651.1	TSL:1	c.544G>A	p.Gly182Ser	missense	Exon 2 of 2	ENSP00000454100.1	Q96BM1
	ANKRD9	ENST00000560748.5	TSL:2	c.544G>A	p.Gly182Ser	missense	Exon 3 of 3	ENSP00000453650.1	Q96BM1

Frequencies

GnomAD3 genomes AF: 0.0000135 AC: 2 AN: 148648 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000294

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000150

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000170 AC: 2 AN: 1174804 Hom.: 0 Cov.: 30 AF XY: 0.00000173 AC XY: 1 AN XY: 577380

African (AFR) AF: 0.00 AC: 0 AN: 21502

American (AMR) AF: 0.00 AC: 0 AN: 12134

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16122

East Asian (EAS) AF: 0.00 AC: 0 AN: 19632

South Asian (SAS) AF: 0.00 AC: 0 AN: 61204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28846

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3188

European-Non Finnish (NFE) AF: 0.00000207 AC: 2 AN: 966738

Other (OTH) AF: 0.00 AC: 0 AN: 45438

GnomAD4 genome AF: 0.0000135 AC: 2 AN: 148648 Hom.: 0 Cov.: 32 AF XY: 0.0000276 AC XY: 2 AN XY: 72440

African (AFR) AF: 0.00 AC: 0 AN: 41120

American (AMR) AF: 0.00 AC: 0 AN: 14940

Ashkenazi Jewish (ASJ) AF: 0.000294 AC: 1 AN: 3406

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9282

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000150 AC: 1 AN: 66644

Other (OTH) AF: 0.00 AC: 0 AN: 2050

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.86	D
M_CAP	Pathogenic	0.49	D
MetaRNN	Pathogenic	0.91	D
MetaSVM	Benign	-0.46	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		5.1
PrimateAI	Pathogenic	0.95	D
PROVEAN	Pathogenic	-5.2	D
REVEL	Uncertain	0.36
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.91	P
Vest4		0.58
MutPred		0.83		Gain of phosphorylation at G182 (P = 0.0876)
MVP		0.82
MPC		2.5
ClinPred		1.0	D
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.82
gMVP		0.67
Mutation Taster		=51/49	polymorphism

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

Other links and lift over

dbSNP: rs1396147502; hg19: chr14-102973683;