22-39018377-G-T

Variant names:

• chr22-39018377-G-T
• rs112120857
• NM_014508.3:c.563G>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014508.3(APOBEC3C):​c.563G>T​(p.Ser188Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00396 in 1,613,764 control chromosomes in the GnomAD database, including 226 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (118 hom., cov: 31)
  • Exomes 𝑓: 0.0022 (108 hom.)
• Consequence: APOBEC3C NM_014508.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.40

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.001642853).
• BP6: Variant 22-39018377-G-T is Benign according to our data. Variant chr22-39018377-G-T is described in ClinVar as [Benign]. Clinvar id is 710831.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC3C	NM_014508.3	c.563G>T	p.Ser188Ile	missense_variant	Exon 4 of 4	ENST00000361441.5	NP_055323.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOBEC3C	ENST00000361441.5	c.563G>T	p.Ser188Ile	missense_variant	Exon 4 of 4	1	NM_014508.3	ENSP00000355340.3
ENSG00000284554	ENST00000381568.9	c.17+3998G>T		intron_variant	Intron 1 of 6	1		ENSP00000370980.4
APOBEC3C	ENST00000428892.1	n.*220G>T		non_coding_transcript_exon_variant	Exon 3 of 3	3		ENSP00000390855.1
APOBEC3C	ENST00000428892.1	n.*220G>T		3_prime_UTR_variant	Exon 3 of 3	3		ENSP00000390855.1

Frequencies

GnomAD3 genomes AF: 0.0205 AC: 3119 AN: 152118 Hom.: 118 Cov.: 31

Gnomad AFR AF: 0.0710

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00733

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: 0.000485

Gnomad OTH AF: 0.0168

GnomAD3 exomes AF: 0.00545 AC: 1367 AN: 250948 Hom.: 45 AF XY: 0.00387 AC XY: 525 AN XY: 135784

Gnomad AFR exome AF: 0.0729

Gnomad AMR exome AF: 0.00373

Gnomad ASJ exome AF: 0.0000995

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000370

Gnomad OTH exome AF: 0.00279

GnomAD4 exome AF: 0.00223 AC: 3261 AN: 1461528 Hom.: 108 Cov.: 32 AF XY: 0.00189 AC XY: 1372 AN XY: 727090

Gnomad4 AFR exome AF: 0.0716

Gnomad4 AMR exome AF: 0.00421

Gnomad4 ASJ exome AF: 0.0000766

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000243

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000307

Gnomad4 OTH exome AF: 0.00474

GnomAD4 genome AF: 0.0205 AC: 3128 AN: 152236 Hom.: 118 Cov.: 31 AF XY: 0.0199 AC XY: 1481 AN XY: 74432

Gnomad4 AFR AF: 0.0710

Gnomad4 AMR AF: 0.00732

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000485

Gnomad4 OTH AF: 0.0166

Alfa AF: 0.00979 Hom.: 21

Bravo AF: 0.0230

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.0726 AC: 320

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.00688 AC: 835

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000711

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 17, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.026
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.55
DANN	Benign	0.67
DEOGEN2	Benign	0.040	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.00086	N
LIST_S2	Benign	0.37	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-3.5	N
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	5.0	N
REVEL	Benign	0.19
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.20
MVP		0.24
MPC		0.18
ClinPred		0.0029	T
GERP RS		0.95
Varity_R		0.15
gMVP		0.052

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs112120857; hg19: chr22-39414382;