Genetic Variant APOBEC3C:p.Cys70Trp (chr22-39017801-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014508.3(APOBEC3C):c.210C>G(p.Cys70Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,676 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

APOBEC3C
NM_014508.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.06

Variant links:

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]

APOBEC3C links:

ENSG00000284554 (HGNC:):

ENSG00000284554 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC3C	NM_014508.3 link	c.210C>G	p.Cys70Trp	missense_variant	Exon 3 of 4	ENST00000361441.5	NP_055323.2	Q9NRW3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
APOBEC3C	ENST00000361441.5 link	c.210C>G	p.Cys70Trp	missense_variant	Exon 3 of 4	1	NM_014508.3	ENSP00000355340.3	Q9NRW3
ENSG00000284554	ENST00000381568.9 link	c.17+3422C>G		intron_variant	Intron 1 of 6	1		ENSP00000370980.4
APOBEC3C	ENST00000428892.1 link	n.53C>G		non_coding_transcript_exon_variant	Exon 2 of 3	3		ENSP00000390855.1	F8WB92

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461676

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727142

show subpopulations

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 20, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.210C>G (p.C70W) alteration is located in exon 3 (coding exon 3) of the APOBEC3C gene. This alteration results from a C to G substitution at nucleotide position 210, causing the cysteine (C) at amino acid position 70 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Benign

-0.030

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.68

DEOGEN2

Benign

0.19

Eigen

Benign

0.015

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.67

M_CAP

Uncertain

0.099

MetaRNN

Uncertain

0.69

MetaSVM

Uncertain

-0.033

MutationAssessor

Uncertain

2.9

PrimateAI

Benign

0.33

PROVEAN

Pathogenic

-7.5

REVEL

Uncertain

0.37

Sift

Uncertain

0.020

Sift4G

Benign

0.069

Polyphen

1.0

Vest4

0.30

MutPred

0.64

Loss of stability (P = 0.0889);

MVP

0.91

MPC

0.75

ClinPred

0.86

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.57

gMVP

0.50

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over