1-183647791-T-A

Variant names:

• chr1-183647791-T-A
• rs1174657
• NM_203454.3:c.991A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_203454.3(APOBEC4):​c.991A>T​(p.Lys331*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: APOBEC4 NM_203454.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0370
• Publications: 40 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203454.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOBEC4	NM_203454.3	MANE Select	c.991A>T	p.Lys331*	stop_gained	Exon 2 of 2	NP_982279.1
	RGL1	NM_015149.6		c.-33+11290T>A		intron	N/A	NP_055964.3
	RGL1	NM_001297669.3		c.-143+11290T>A		intron	N/A	NP_001284598.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOBEC4	ENST00000308641.6	TSL:1 MANE Select	c.991A>T	p.Lys331*	stop_gained	Exon 2 of 2	ENSP00000310622.4
	RGL1	ENST00000304685.8	TSL:1	c.-33+11290T>A		intron	N/A	ENSP00000303192.3
	APOBEC4	ENST00000481562.1	TSL:3	n.252A>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 58

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 42729

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	34
DANN	Benign	0.90
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.12	N
PhyloP100		0.037
Vest4		0.11
GERP RS		-0.47
Mutation Taster		=87/113	disease causing

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

Other links and lift over

dbSNP: rs1174657; hg19: chr1-183616926;