22-39045213-C-A

Position:

• chr22-39045213-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145298.6(APOBEC3F):​c.444C>A​(p.Asp148Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000135 in 1,613,928 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (1 hom.)
• Consequence: APOBEC3F NM_145298.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.504

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1007683).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOBEC3F	NM_145298.6	c.444C>A	p.Asp148Glu	missense_variant	3/7	ENST00000308521.10	NP_660341.2
APOBEC3F	XM_047441184.1	c.444C>A	p.Asp148Glu	missense_variant	3/6		XP_047297140.1
APOBEC3F	XM_047441185.1	c.444C>A	p.Asp148Glu	missense_variant	3/5		XP_047297141.1
APOBEC3F	XM_017028642.3	c.444C>A	p.Asp148Glu	missense_variant	3/5		XP_016884131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOBEC3F	ENST00000308521.10	c.444C>A	p.Asp148Glu	missense_variant	3/7	1	NM_145298.6	ENSP00000309749	P1
APOBEC3F	ENST00000476513.1	n.30C>A		non_coding_transcript_exon_variant	1/3	3
APOBEC3F	ENST00000491387.1			downstream_gene_variant		4

Frequencies

GnomAD3 genomes AF: 0.000335 AC: 51 AN: 152062 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00288

GnomAD3 exomes AF: 0.000148 AC: 37 AN: 250520 Hom.: 0 AF XY: 0.000162 AC XY: 22 AN XY: 135634

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.000497

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000150

Gnomad OTH exome AF: 0.000492

GnomAD4 exome AF: 0.000115 AC: 168 AN: 1461748 Hom.: 1 Cov.: 34 AF XY: 0.000128 AC XY: 93 AN XY: 727146

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000358

Gnomad4 ASJ exome AF: 0.000880

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000927

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000809

Gnomad4 OTH exome AF: 0.000232

GnomAD4 genome AF: 0.000329 AC: 50 AN: 152180 Hom.: 0 Cov.: 32 AF XY: 0.000336 AC XY: 25 AN XY: 74390

Gnomad4 AFR AF: 0.0000482

Gnomad4 AMR AF: 0.00164

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00285

Alfa AF: 0.000144 Hom.: 1

Bravo AF: 0.000363

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.000115 AC: 14

EpiCase AF: 0.000545

EpiControl AF: 0.000296

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 18, 2022

The c.444C>A (p.D148E) alteration is located in exon 3 (coding exon 3) of the APOBEC3F gene. This alteration results from a C to A substitution at nucleotide position 444, causing the aspartic acid (D) at amino acid position 148 to be replaced by a glutamic acid (E). 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	Uncertain	0.54
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	6.6
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0049	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Uncertain	2.5	M
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.11
Sift	Benign	0.053	T
Sift4G	Benign	0.35	T
Polyphen		1.0	D
Vest4		0.092
MutPred		0.48		Loss of sheet (P = 0.1501);
MVP		0.58
MPC		1.0
ClinPred		0.11	T
GERP RS		-2.6
Varity_R		0.12
gMVP		0.045

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs201454313; hg19: chr22-39441218;