12-7652559-G-C

Variant names:

• chr12-7652559-G-C
• rs143430302
• NM_001644.5:c.321C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001644.5(APOBEC1):​c.321C>G​(p.His107Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: APOBEC1 NM_001644.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.109

Genes affected

APOBEC1 (HGNC:604): (apolipoprotein B mRNA editing enzyme catalytic subunit 1) This gene encodes a member of the cytidine deaminase enzyme family. The encoded protein forms a multiple-protein editing holoenzyme with APOBEC1 complementation factor (ACF) and APOBEC1 stimulating protein (ASP). This holoenzyme is involved in the editing of C-to-U nucleotide bases in apolipoprotein B and neurofibromatosis-1 mRNAs. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30319422).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC1	NM_001644.5	c.321C>G	p.His107Gln	missense_variant	Exon 3 of 5	ENST00000229304.5	NP_001635.2
APOBEC1	NM_001304566.1	c.321C>G	p.His107Gln	missense_variant	Exon 4 of 6		NP_001291495.1
APOBEC1	NM_005889.4	c.186C>G	p.His62Gln	missense_variant	Exon 2 of 4		NP_005880.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOBEC1	ENST00000229304.5	c.321C>G	p.His107Gln	missense_variant	Exon 3 of 5	1	NM_001644.5	ENSP00000229304.4
APOBEC1	ENST00000467171.2	n.*182C>G		non_coding_transcript_exon_variant	Exon 2 of 4	1		ENSP00000436415.2
APOBEC1	ENST00000467171.2	n.*182C>G		3_prime_UTR_variant	Exon 2 of 4	1		ENSP00000436415.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251472 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135918

Gnomad AFR exome AF: 0.0000615

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: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 22, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.321C>G (p.H107Q) alteration is located in exon 3 (coding exon 3) of the APOBEC1 gene. This alteration results from a C to G substitution at nucleotide position 321, causing the histidine (H) at amino acid position 107 to be replaced by a glutamine (Q). 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	0.25
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	3.7
DANN	Benign	0.88
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Pathogenic	3.4	M
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Benign	0.13
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.027	D
Polyphen		0.22	B
Vest4		0.22
MutPred		0.69		Gain of MoRF binding (P = 0.261);
MVP		0.63
MPC		0.91
ClinPred		0.26	T
GERP RS		-1.0
Varity_R		0.51
gMVP		0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs143430302; hg19: chr12-7805155;