rs112120857

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr22-39018377-G-T
• chr22-39018377-G-C

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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
• Publications: 21 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: Benign. The variant received -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 VariationId 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.

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.563G>T	p.Ser188Ile	missense	Exon 4 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.563G>T	p.Ser188Ile	missense	Exon 4 of 4	ENSP00000355340.3	Q9NRW3
	ENSG00000284554	ENST00000381568.9	TSL:1	c.17+3998G>T		intron	N/A	ENSP00000370980.4
	APOBEC3C	ENST00000869067.1		c.356G>T	p.Ser119Ile	missense	Exon 4 of 4	ENSP00000539126.1

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

GnomAD2 exomes AF: 0.00545 AC: 1367 AN: 250948 AF XY: 0.00387

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 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

African (AFR) AF: 0.0716 AC: 2396 AN: 33462

American (AMR) AF: 0.00421 AC: 188 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.0000766 AC: 2 AN: 26110

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39692

South Asian (SAS) AF: 0.000243 AC: 21 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00434 AC: 25 AN: 5766

European-Non Finnish (NFE) AF: 0.000307 AC: 341 AN: 1111768

Other (OTH) AF: 0.00474 AC: 286 AN: 60376

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

African (AFR) AF: 0.0710 AC: 2948 AN: 41516

American (AMR) AF: 0.00732 AC: 112 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000485 AC: 33 AN: 68008

Other (OTH) AF: 0.0166 AC: 35 AN: 2104

Alfa AF: 0.0105 Hom.: 23

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		2.4
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
Mutation Taster		=95/5	polymorphism (auto)

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

Other links and lift over

dbSNP: rs112120857; hg19: chr22-39414382;