rs10911390

chr1-183647749-C-Gchr1-183647749-C-T

Variant summary

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

The NM_203454.3(APOBEC4):c.1033G>C(p.Val345Leu) 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. 15/21 in silico tools predict a benign 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. V345M) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: APOBEC4 NM_203454.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.238

Genes affected

APOBEC4 (HGNC:32152): (apolipoprotein B mRNA editing enzyme catalytic polypeptide like 4) This gene encodes a member of the AID/APOBEC family of polynucleotide (deoxy)cytidine deaminases, which convert cytidine to uridine. Other AID/APOBEC family members are involved in mRNA editing, somatic hypermutation and recombination of immunoglobulin genes, and innate immunity to retroviral infection. [provided by RefSeq, Jul 2008]

RGL1 (HGNC:30281): (ral guanine nucleotide dissociation stimulator like 1) Predicted to be involved in regulation of catalytic activity. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

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=0.35838303).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOBEC4	NM_203454.3	c.1033G>C	p.Val345Leu	missense_variant	2/2	ENST00000308641.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOBEC4	ENST00000308641.6	c.1033G>C	p.Val345Leu	missense_variant	2/2	1	NM_203454.3	P1
RGL1	ENST00000304685.8	c.-33+11248C>G		intron_variant		1
APOBEC4	ENST00000481562.1	n.294G>C		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
Cadd	Benign	5.2
Dann	Benign	0.91
DEOGEN2	Benign	0.046	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	0.00022	P;P;P;P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.057
Sift	Benign	0.052	T
Sift4G	Benign	0.10	T
Polyphen		0.032	B
Vest4		0.057
MutPred		0.12		Loss of sheet (P = 0.0084);
MVP		0.13
MPC		0.11
ClinPred		0.089	T
GERP RS		3.3
Varity_R		0.13
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs10911390; hg19: chr1-183616884;