10-122576624-GC-TT

Variant names:

• chr10-122576624-GC-TT
• NM_001377530.1:c.509_510delGCinsTT
• DMBT1 p.Arg170Leu

Variant summary

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

The NM_001377530.1(DMBT1):​c.509_510delGCinsTT​(p.Arg170Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. R170H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DMBT1 NM_001377530.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 0 publications found

Genes affected

DMBT1 (HGNC:2926): (deleted in malignant brain tumors 1) Loss of sequences from human chromosome 10q has been associated with the progression of human cancers. This gene was originally isolated based on its deletion in a medulloblastoma cell line. This gene is expressed with transcripts of 6.0, 7.5, and 8.0 kb in fetal lung and with one transcript of 8.0 kb in adult lung, although the 7.5 kb transcript has not been characterized. The encoded protein precursor is a glycoprotein containing multiple scavenger receptor cysteine-rich (SRCR) domains separated by SRCR-interspersed domains (SID). Transcript variant 2 (8.0 kb) has been shown to bind surfactant protein D independently of carbohydrate recognition. This indicates that DMBT1 may not be a classical tumor suppressor gene, but rather play a role in the interaction of tumor cells and the immune system. [provided by RefSeq, Mar 2016]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377530.1. 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
	DMBT1	NM_001377530.1	MANE Select	c.509_510delGCinsTT	p.Arg170Leu	missense	N/A	NP_001364459.1	Q9UGM3-6
	DMBT1	NM_007329.3		c.509_510delGCinsTT	p.Arg170Leu	missense	N/A	NP_015568.2	Q9UGM3-1
	DMBT1	NM_001320644.2		c.509_510delGCinsTT	p.Arg170Leu	missense	N/A	NP_001307573.1	A0A590UJ76

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMBT1	ENST00000338354.10	TSL:1 MANE Select	c.509_510delGCinsTT	p.Arg170Leu	missense	N/A	ENSP00000342210.4	Q9UGM3-6
	DMBT1	ENST00000344338.7	TSL:1	c.509_510delGCinsTT	p.Arg170Leu	missense	N/A	ENSP00000343175.3	Q9UGM3-3
	DMBT1	ENST00000330163.8	TSL:1	c.509_510delGCinsTT	p.Arg170Leu	missense	N/A	ENSP00000327747.4	Q9UGM3-2

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.3

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: chr10-124336140;