19-40775652-CG-GT

Variant names:

• chr19-40775652-CG-GT
• NM_006533.4:c.110_111delCGinsGT
• MIA p.Ala37Gly

Variant summary

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

The NM_006533.4(MIA):​c.110_111delCGinsGT​(p.Ala37Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. A37V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MIA NM_006533.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.54
• Publications: 0 publications found

Genes affected

MIA (HGNC:7076): (MIA SH3 domain containing) Predicted to enable growth factor activity. Predicted to be involved in extracellular matrix organization. Predicted to act upstream of or within cell-matrix adhesion. Predicted to be located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006533.4. 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
	MIA	NM_006533.4	MANE Select	c.110_111delCGinsGT	p.Ala37Gly	missense	N/A	NP_006524.1	Q16674-1
	MIA	NM_001202553.2		c.110_111delCGinsGT	p.Ala37Gly	missense	N/A	NP_001189482.1	Q16674-1
	MIA-RAB4B	NR_037775.1		n.116_117delCGinsGT		non_coding_transcript_exon	Exon 1 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIA	ENST00000263369.4	TSL:1 MANE Select	c.110_111delCGinsGT	p.Ala37Gly	missense	N/A	ENSP00000263369.2	Q16674-1
	MIA-RAB4B	ENST00000600729.2	TSL:5	n.110_111delCGinsGT		non_coding_transcript_exon	Exon 2 of 11	ENSP00000472384.1	W4VSR3
	MIA	ENST00000594436.5	TSL:2	c.110_111delCGinsGT	p.Ala37Gly	missense	N/A	ENSP00000470129.1	Q16674-1

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 v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.5

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-41281557;