22-39017869-C-T

Variant names:

• chr22-39017869-C-T
• rs928893236
• NM_014508.3:c.278C>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.278C>T​(p.Ser93Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S93Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: APOBEC3C NM_014508.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.81
• Publications: 1 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, 0.988

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.278C>T	p.Ser93Phe	missense	Exon 3 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.278C>T	p.Ser93Phe	missense	Exon 3 of 4	ENSP00000355340.3	Q9NRW3
	ENSG00000284554	ENST00000381568.9	TSL:1	c.17+3490C>T		intron	N/A	ENSP00000370980.4
	APOBEC3C	ENST00000869067.1		c.175-104C>T		intron	N/A	ENSP00000539126.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Benign	22
DANN	Benign	0.76
DEOGEN2	Benign	0.33	T
Eigen	Uncertain	0.37
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.067	N
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.061	D
MetaRNN	Pathogenic	0.99	D
MetaSVM	Uncertain	0.093	D
MutationAssessor	Pathogenic	3.6	H
PhyloP100		4.8
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Uncertain	0.54
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.81
MutPred		0.96		Gain of sheet (P = 0.1208)
MVP		0.88
MPC		0.68
ClinPred		0.90	D
GERP RS		2.0
Varity_R		0.70
gMVP		0.45
Mutation Taster		=75/25	polymorphism

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

Other links and lift over

dbSNP: rs928893236; hg19: chr22-39413874;