22-39015735-G-T

Variant names:

• chr22-39015735-G-T
• NM_014508.3:c.158G>T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_014508.3(APOBEC3C):​c.158G>T​(p.Gly53Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: APOBEC3C NM_014508.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.35
• Publications: 0 publications found

Genes affected

APOBEC3C (HGNC:17353): (apolipoprotein B mRNA editing enzyme catalytic subunit 3C) This gene is a member of the cytidine deaminase gene family. It is one of seven related genes or pseudogenes found in a cluster thought to result from gene duplication, on chromosome 22. Members of the cluster encode proteins that are structurally and functionally related to the C to U RNA-editing cytidine deaminase APOBEC1. It is thought that the proteins may be RNA editing enzymes and have roles in growth or cell cycle control. [provided by RefSeq, Jul 2008]

ENSG00000284554 (HGNC:):

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.97

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014508.3. 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
	APOBEC3C	NM_014508.3	MANE Select	c.158G>T	p.Gly53Val	missense	Exon 2 of 4	NP_055323.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOBEC3C	ENST00000361441.5	TSL:1 MANE Select	c.158G>T	p.Gly53Val	missense	Exon 2 of 4	ENSP00000355340.3	Q9NRW3
	ENSG00000284554	ENST00000381568.9	TSL:1	c.17+1356G>T		intron	N/A	ENSP00000370980.4
	APOBEC3C	ENST00000869067.1		c.158G>T	p.Gly53Val	missense	Exon 2 of 4	ENSP00000539126.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

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	Uncertain	0.54
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.099
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.12	N
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.048	D
MetaRNN	Pathogenic	0.97	D
MetaSVM	Uncertain	0.099	D
MutationAssessor	Pathogenic	3.4	M
PhyloP100		2.4
PrimateAI	Benign	0.34	T
PROVEAN	Pathogenic	-6.5	D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.56
MutPred		0.88		Gain of sheet (P = 0.1208)
MVP		0.94
MPC		0.73
ClinPred		0.95	D
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.71
gMVP		0.62
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

hg19: chr22-39411740;