rs16861381

Variant names:

• chr1-183647883-T-A
• NM_203454.3:c.899A>T

Your query was ambiguous. Multiple possible variants found:

• chr1-183647883-T-A
• chr1-183647883-T-C

Variant summary

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

The NM_203454.3(APOBEC4):​c.899A>T​(p.Asp300Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 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. D300G) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: APOBEC4 NM_203454.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.958

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC4	NM_203454.3	c.899A>T	p.Asp300Val	missense_variant	Exon 2 of 2	ENST00000308641.6	NP_982279.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOBEC4	ENST00000308641.6	c.899A>T	p.Asp300Val	missense_variant	Exon 2 of 2	1	NM_203454.3	ENSP00000310622.4
RGL1	ENST00000304685.8	c.-33+11382T>A		intron_variant	Intron 1 of 18	1		ENSP00000303192.3
APOBEC4	ENST00000481562.1	n.246-86A>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461890 Hom.: 0 Cov.: 66 AF XY: 0.00 AC XY: 0 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	9.7
DANN	Benign	0.60
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0070	T
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.055
Sift	Benign	0.070	T
Sift4G	Benign	0.20	T
Polyphen		0.57	P
Vest4		0.35
MutPred		0.26		Gain of catalytic residue at D300 (P = 0.1207);
MVP		0.29
MPC		0.32
ClinPred		0.36	T
GERP RS		2.9
Varity_R		0.16
gMVP		0.28

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-183617018;