rs534595473

Variant names:

• chr6-41061748-C-G
• NM_006789.4:c.552C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-41061748-C-G
• chr6-41061748-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_006789.4(APOBEC2):​c.552C>G​(p.Phe184Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: APOBEC2 NM_006789.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.85

Genes affected

APOBEC2 (HGNC:605): (apolipoprotein B mRNA editing enzyme catalytic subunit 2) Enables cytidine deaminase activity and identical protein binding activity. Involved in DNA demethylation. Acts upstream of or within cytidine to uridine editing. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

OARD1 (HGNC:21257): (O-acyl-ADP-ribose deacylase 1) The protein encoded by this gene is a deacylase that can convert O-acetyl-ADP-ribose to ADP-ribose and acetate, O-propionyl-ADP-ribose to ADP-ribose and propionate, and O-butyryl-ADP-ribose to ADP-ribose and butyrate. The ADP-ribose product is able to inhibit these reactions through a competitive feedback loop. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.944

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC2	NM_006789.4	c.552C>G	p.Phe184Leu	missense_variant	Exon 2 of 3	ENST00000244669.3	NP_006780.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOBEC2	ENST00000244669.3	c.552C>G	p.Phe184Leu	missense_variant	Exon 2 of 3	1	NM_006789.4	ENSP00000244669.2
OARD1	ENST00000482853.5	n.144+8328G>C		intron_variant	Intron 2 of 4	2		ENSP00000420472.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461892 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727246

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.89	D
M_CAP	Uncertain	0.099	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Uncertain	2.7	M
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.012	D
Polyphen		1.0	D
Vest4		0.92
MutPred		0.81		Gain of MoRF binding (P = 0.1634);
MVP		0.77
MPC		0.39
ClinPred		0.99	D
GERP RS		5.9
Varity_R		0.96
gMVP		0.73

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-41029487;