22-39018327-G-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_014508.3(APOBEC3C):​c.513G>C​(p.Trp171Cys) 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 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

APOBEC3C
NM_014508.3 missense

Scores

4
8
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.40
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]

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ACMG classification

Classification made for transcript

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, 0.955

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
APOBEC3CNM_014508.3 linkc.513G>C p.Trp171Cys missense_variant Exon 4 of 4 ENST00000361441.5 NP_055323.2 Q9NRW3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
APOBEC3CENST00000361441.5 linkc.513G>C p.Trp171Cys missense_variant Exon 4 of 4 1 NM_014508.3 ENSP00000355340.3 Q9NRW3
ENSG00000284554ENST00000381568.9 linkc.17+3948G>C intron_variant Intron 1 of 6 1 ENSP00000370980.4
APOBEC3CENST00000428892.1 linkn.*170G>C non_coding_transcript_exon_variant Exon 3 of 3 3 ENSP00000390855.1 F8WB92
APOBEC3CENST00000428892.1 linkn.*170G>C 3_prime_UTR_variant Exon 3 of 3 3 ENSP00000390855.1 F8WB92

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461864
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
727238
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 13, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.513G>C (p.W171C) alteration is located in exon 4 (coding exon 4) of the APOBEC3C gene. This alteration results from a G to C substitution at nucleotide position 513, causing the tryptophan (W) at amino acid position 171 to be replaced by a cysteine (C). 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
0.83
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.040
CADD
Benign
21
DANN
Benign
0.96
DEOGEN2
Benign
0.23
T
Eigen
Uncertain
0.24
Eigen_PC
Benign
-0.031
FATHMM_MKL
Benign
0.61
D
LIST_S2
Uncertain
0.90
D
M_CAP
Benign
0.071
D
MetaRNN
Pathogenic
0.96
D
MetaSVM
Benign
-0.46
T
MutationAssessor
Pathogenic
3.2
M
PrimateAI
Uncertain
0.51
T
PROVEAN
Pathogenic
-12
D
REVEL
Uncertain
0.40
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0020
D
Polyphen
1.0
D
Vest4
0.51
MutPred
0.85
Gain of catalytic residue at P170 (P = 0.0073);
MVP
0.87
MPC
0.82
ClinPred
1.0
D
GERP RS
2.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.75
gMVP
0.54

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: chr22-39414332; API