rs2074533

Variant names:

• chr12-47740912-T-A
• rs2074533
• NM_001098531.4:c.2049+3A>T

Your query was ambiguous. Multiple possible variants found:

• chr12-47740912-T-A
• chr12-47740912-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001098531.4(RAPGEF3):​c.2049+3A>T variant causes a splice region, intron 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. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as (no stars).

• Frequency: Genomes: not found (cov: 34)
• Consequence: RAPGEF3 NM_001098531.4 splice_region, intron
• Scores: Splicing: ADA: 0.5427
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.168
• Publications: 17 publications found

Genes affected

RAPGEF3 (HGNC:16629): (Rap guanine nucleotide exchange factor 3) Enables guanyl-nucleotide exchange factor activity and protein domain specific binding activity. Involved in several processes, including positive regulation of protein modification process; regulation of actin cytoskeleton organization; and regulation of syncytium formation by plasma membrane fusion. Located in filopodium; lamellipodium; and microvillus. Colocalizes with cortical actin cytoskeleton and plasma membrane. Biomarker of congestive heart failure. [provided by Alliance of Genome Resources, Apr 2022]

RPAP3-DT (HGNC:55477): (RPAP3 divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098531.4. 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
	RAPGEF3	NM_001098531.4	MANE Select	c.2049+3A>T		splice_region intron	N/A	NP_001092001.2
	RAPGEF3	NM_001098532.2		c.1923+3A>T		splice_region intron	N/A	NP_001092002.1
	RAPGEF3	NM_006105.5		c.1923+3A>T		splice_region intron	N/A	NP_006096.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAPGEF3	ENST00000449771.7	TSL:2 MANE Select	c.2049+3A>T		splice_region intron	N/A	ENSP00000395708.2
	RAPGEF3	ENST00000389212.7	TSL:2	c.2049+3A>T		splice_region intron	N/A	ENSP00000373864.3
	RAPGEF3	ENST00000549151.5	TSL:5	c.1923+3A>T		splice_region intron	N/A	ENSP00000448619.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 82

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	10
DANN	Benign	0.79
PhyloP100		-0.17

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.54
dbscSNV1_RF	Benign	0.35
SpliceAI score (max)		0.48		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.48		Position offset: 14

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2074533; hg19: chr12-48134695;