14-102507132-C-A

Variant names:

• chr14-102507132-C-A
• rs1489673164
• NM_152326.4:c.758G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_152326.4(ANKRD9):​c.758G>T​(p.Gly253Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. G253D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANKRD9 NM_152326.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.50
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.758G>T	p.Gly253Val	missense	Exon 4 of 4	NP_689539.1	Q96BM1
	ANKRD9	NM_001348651.2		c.758G>T	p.Gly253Val	missense	Exon 4 of 4	NP_001335580.1	Q96BM1
	ANKRD9	NM_001348652.2		c.758G>T	p.Gly253Val	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.758G>T	p.Gly253Val	missense	Exon 4 of 4	ENSP00000286918.4	Q96BM1
	ANKRD9	ENST00000559651.1	TSL:1	c.758G>T	p.Gly253Val	missense	Exon 2 of 2	ENSP00000454100.1	Q96BM1
	ANKRD9	ENST00000560748.5	TSL:2	c.758G>T	p.Gly253Val	missense	Exon 3 of 3	ENSP00000453650.1	Q96BM1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1321848 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 649822

African (AFR) AF: 0.00 AC: 0 AN: 26636

American (AMR) AF: 0.00 AC: 0 AN: 26214

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22368

East Asian (EAS) AF: 0.00 AC: 0 AN: 30692

South Asian (SAS) AF: 0.00 AC: 0 AN: 70848

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32738

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5172

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1052086

Other (OTH) AF: 0.00 AC: 0 AN: 55094

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.059	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.036	T
Eigen	Benign	0.079
Eigen_PC	Benign	0.083
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.73	T
M_CAP	Pathogenic	0.96	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.32	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.5
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.32
Sift	Benign	0.18	T
Sift4G	Benign	0.15	T
Polyphen		0.80	P
Vest4		0.11
MutPred		0.25		Loss of disorder (P = 0.0402)
MVP		0.95
MPC		2.3
ClinPred		0.45	T
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.30
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1489673164; hg19: chr14-102973469;