Variant 22-39044965-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_145298.6(APOBEC3F):c.196G>C(p.Ala66Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000831 in 1,613,418 control chromosomes in the GnomAD database, including 1 homozygotes. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000088 ( 1 hom. )

Consequence

APOBEC3F
NM_145298.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.75

Variant links:

Genes affected

APOBEC3F (HGNC:17356): (apolipoprotein B mRNA editing enzyme catalytic subunit 3F) 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. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

APOBEC3F 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/exons	MANE	Protein
APOBEC3F	NM_145298.6 linkuse as main transcript	c.196G>C	p.Ala66Pro	missense_variant	3/7	ENST00000308521.10	NP_660341.2
APOBEC3F	XM_047441184.1 linkuse as main transcript	c.196G>C	p.Ala66Pro	missense_variant	3/6		XP_047297140.1
APOBEC3F	XM_047441185.1 linkuse as main transcript	c.196G>C	p.Ala66Pro	missense_variant	3/5		XP_047297141.1
APOBEC3F	XM_017028642.3 linkuse as main transcript	c.196G>C	p.Ala66Pro	missense_variant	3/5		XP_016884131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOBEC3F	ENST00000308521.10 linkuse as main transcript	c.196G>C	p.Ala66Pro	missense_variant	3/7	1	NM_145298.6	ENSP00000309749	P1	Q8IUX4-1
APOBEC3F	ENST00000491387.1 linkuse as main transcript	n.343G>C		non_coding_transcript_exon_variant	3/3	4

Frequencies

GnomAD3 genomes

AF:

0.0000330

AC:

AN:

151590

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000955

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000915

AC:

AN:

251434

Hom.:

AF XY:

0.000118

AC XY:

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000323

Gnomad NFE exome

AF:

0.000114

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.0000882

AC:

129

AN:

1461828

Hom.:

Cov.:

AF XY:

0.0000839

AC XY:

AN XY:

727210

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:

0.000805

Gnomad4 NFE exome

AF:

0.0000683

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.0000330

AC:

AN:

151590

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

73980

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000955

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.0000501

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000906

AC:

EpiCase

AF:

0.000164

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

The c.196G>C (p.A66P) alteration is located in exon 3 (coding exon 3) of the APOBEC3F gene. This alteration results from a G to C substitution at nucleotide position 196, causing the alanine (A) at amino acid position 66 to be replaced by a proline (P). 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

Benign

0.24

BayesDel_addAF

Benign

-0.044

BayesDel_noAF

Uncertain

-0.070

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.0081

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.61

M_CAP

Benign

0.045

MetaRNN

Uncertain

0.53

MetaSVM

Uncertain

-0.14

MutationAssessor

Benign

1.7

MutationTaster

Benign

1.0

N;D

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.5

REVEL

Uncertain

0.48

Sift

Benign

0.41

Sift4G

Benign

0.22

Polyphen

1.0

Vest4

0.24

MutPred

0.79

Gain of disorder (P = 0.0361);

MVP

0.81

MPC

1.3

ClinPred

0.089

GERP RS

0.20

Varity_R

0.43

gMVP

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over