chr14-102507132-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152326.4(ANKRD9):​c.758G>A​(p.Gly253Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANKRD9 NM_152326.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23527241).

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>A	p.Gly253Asp	missense	Exon 4 of 4	NP_689539.1	Q96BM1
	ANKRD9	NM_001348651.2		c.758G>A	p.Gly253Asp	missense	Exon 4 of 4	NP_001335580.1	Q96BM1
	ANKRD9	NM_001348652.2		c.758G>A	p.Gly253Asp	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>A	p.Gly253Asp	missense	Exon 4 of 4	ENSP00000286918.4	Q96BM1
	ANKRD9	ENST00000559651.1	TSL:1	c.758G>A	p.Gly253Asp	missense	Exon 2 of 2	ENSP00000454100.1	Q96BM1
	ANKRD9	ENST00000560748.5	TSL:2	c.758G>A	p.Gly253Asp	missense	Exon 3 of 3	ENSP00000453650.1	Q96BM1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152006 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

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 AF: 0.00000658 AC: 1 AN: 152006 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74268

African (AFR) AF: 0.00 AC: 0 AN: 41424

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10534

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67974

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Benign	0.10
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0050	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.63	T
M_CAP	Pathogenic	0.85	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	0.88	L
PhyloP100		2.5
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	0.080	N
REVEL	Uncertain	0.34
Sift	Benign	0.59	T
Sift4G	Benign	0.61	T
Polyphen		0.0010	B
Vest4		0.052
MutPred		0.32		Loss of helix (P = 0.0237)
MVP		0.84
MPC		1.9
ClinPred		0.27	T
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.070
gMVP		0.14
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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;