Genetic Variant DMBT1:p.Ser98Pro (chr10-122576407-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001377530.1(DMBT1):c.292T>C(p.Ser98Pro) variant causes a missense 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

DMBT1
NM_001377530.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.681

Publications

0 publications found

Variant links:

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]

DMBT1 links:

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ACMG classification

Classification was made for transcript

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 (MetaRNN=0.06398931).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DMBT1	NM_001377530.1	MANE Select	c.292T>C	p.Ser98Pro	missense	Exon 7 of 56	NP_001364459.1	Q9UGM3-6
DMBT1	NM_007329.3		c.292T>C	p.Ser98Pro	missense	Exon 7 of 53	NP_015568.2	Q9UGM3-1
DMBT1	NM_001320644.2		c.292T>C	p.Ser98Pro	missense	Exon 7 of 53	NP_001307573.1	A0A590UJ76

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DMBT1	ENST00000338354.10	TSL:1 MANE Select	c.292T>C	p.Ser98Pro	missense	Exon 7 of 56	ENSP00000342210.4	Q9UGM3-6
DMBT1	ENST00000344338.7	TSL:1	c.292T>C	p.Ser98Pro	missense	Exon 7 of 52	ENSP00000343175.3	Q9UGM3-3
DMBT1	ENST00000330163.8	TSL:1	c.292T>C	p.Ser98Pro	missense	Exon 7 of 40	ENSP00000327747.4	Q9UGM3-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.022

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.058

M_CAP

Benign

0.0072

MetaRNN

Benign

0.064

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-0.68

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.020

REVEL

Benign

0.047

Sift

Benign

0.088

Sift4G

Benign

0.27

Polyphen

0.97

Vest4

0.13

MutPred

0.29

Loss of glycosylation at S98 (P = 0.0323)

MVP

0.39

MPC

0.30

ClinPred

0.36

GERP RS

3.3

Varity_R

0.068

gMVP

0.13

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over