ENST00000601627.1:n.118-23337delA

Variant names:

• chr19-40778076-CT-C
• ENST00000600729.2:n.372+998delT

Variant summary

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

The ENST00000600729.2(MIA-RAB4B):​n.372+998delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MIA-RAB4B ENST00000600729.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0150

Genes affected

MIA-RAB4B (HGNC:48352): (MIA-RAB4B readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring MIA (melanoma inhibitory activity) and RAB4B (RAB4B, member RAS oncogene family) genes on chromosome 19. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is therefore unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

RAB4B (HGNC:9782): (RAB4B, member RAS oncogene family) Predicted to enable G protein activity and GTP binding activity. Involved in glucose import. Located in insulin-responsive compartment; perinuclear region of cytoplasm; and recycling endosome. [provided by Alliance of Genome Resources, Apr 2022]

RAB4B-EGLN2 (HGNC:44465): (RAB4B-EGLN2 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring RAB4B (RAB4B, member RAS oncogene family) and EGLN2 (egl nine homolog 2) genes on chromosome 19. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

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
MIA-RAB4B	NR_037775.1	n.378+998delT		intron_variant	Intron 3 of 9
RAB4B	NM_016154.5	c.-299delT		upstream_gene_variant		ENST00000357052.8	NP_057238.3
RAB4B-EGLN2	NR_037791.1	n.-142delT		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIA-RAB4B	ENST00000600729.2	n.372+998delT		intron_variant	Intron 4 of 10	5		ENSP00000472384.1
RAB4B	ENST00000357052.8	c.-299delT		upstream_gene_variant		1	NM_016154.5	ENSP00000349560.2
RAB4B-EGLN2	ENST00000594136.2	n.-299delT		upstream_gene_variant		2		ENSP00000469872.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr19-41283981;