rs3013236

Variant names:

• chr10-122570911-C-A
• rs3013236
• NM_001377530.1:c.161C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-122570911-C-A
• chr10-122570911-C-G
• chr10-122570911-C-T

Variant summary

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

The NM_001377530.1(DMBT1):​c.161C>A​(p.Ser54*) 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 benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DMBT1 NM_001377530.1 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.77
• Publications: 28 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 2 ACMG points.

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

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.161C>A	p.Ser54*	stop_gained	Exon 4 of 56	NP_001364459.1	Q9UGM3-6
	DMBT1	NM_007329.3		c.161C>A	p.Ser54*	stop_gained	Exon 4 of 53	NP_015568.2	Q9UGM3-1
	DMBT1	NM_001320644.2		c.161C>A	p.Ser54*	stop_gained	Exon 4 of 53	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.161C>A	p.Ser54*	stop_gained	Exon 4 of 56	ENSP00000342210.4	Q9UGM3-6
	DMBT1	ENST00000344338.7	TSL:1	c.161C>A	p.Ser54*	stop_gained	Exon 4 of 52	ENSP00000343175.3	Q9UGM3-3
	DMBT1	ENST00000330163.8	TSL:1	c.161C>A	p.Ser54*	stop_gained	Exon 4 of 40	ENSP00000327747.4	Q9UGM3-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 58

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 65074

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Pathogenic	33
DANN	Benign	0.86
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0017	N
PhyloP100		-2.8
Vest4		0.42
GERP RS		-3.1
Mutation Taster		=101/99	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3013236; hg19: chr10-124330427;