Variant 10-122570905-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001377530.1(DMBT1):c.155C>G(p.Ser52Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.015 in 1,613,340 control chromosomes in the GnomAD database, including 1,509 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.057 ( 776 hom., cov: 33)

Exomes 𝑓: 0.011 ( 733 hom. )

Consequence

DMBT1
NM_001377530.1 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.139

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:

DMBT1 (HGNC:):

DMBT1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013635755).

BP6

Variant 10-122570905-C-G is Benign according to our data. Variant chr10-122570905-C-G is described in ClinVar as [Benign]. Clinvar id is 3037372.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMBT1	NM_001377530.1 linkuse as main transcript	c.155C>G	p.Ser52Trp	missense_variant	4/56	ENST00000338354.10	NP_001364459.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMBT1	ENST00000338354.10 linkuse as main transcript	c.155C>G	p.Ser52Trp	missense_variant	4/56	1	NM_001377530.1	ENSP00000342210.4		Q9UGM3-6

Frequencies

GnomAD3 genomes

AF:

0.0572

AC:

8701

AN:

152116

Hom.:

771

Cov.:

show subpopulations

Gnomad AFR

AF:

0.188

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0239

Gnomad ASJ

AF:

0.00951

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00584

Gnomad OTH

AF:

0.0460

GnomAD3 exomes

AF:

0.0172

AC:

4290

AN:

249214

Hom.:

314

AF XY:

0.0140

AC XY:

1893

AN XY:

135198

show subpopulations

Gnomad AFR exome

AF:

0.195

Gnomad AMR exome

AF:

0.0117

Gnomad ASJ exome

AF:

0.00815

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00232

Gnomad FIN exome

AF:

0.000511

Gnomad NFE exome

AF:

0.00567

Gnomad OTH exome

AF:

0.0106

GnomAD4 exome

AF:

0.0106

AC:

15555

AN:

1461106

Hom.:

733

Cov.:

AF XY:

0.00983

AC XY:

7148

AN XY:

726904

show subpopulations

Gnomad4 AFR exome

AF:

0.200

Gnomad4 AMR exome

AF:

0.0130

Gnomad4 ASJ exome

AF:

0.00693

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00235

Gnomad4 FIN exome

AF:

0.000693

Gnomad4 NFE exome

AF:

0.00598

Gnomad4 OTH exome

AF:

0.0183

GnomAD4 genome

AF:

0.0573

AC:

8717

AN:

152234

Hom.:

776

Cov.:

AF XY:

0.0559

AC XY:

4159

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.188

Gnomad4 AMR

AF:

0.0237

Gnomad4 ASJ

AF:

0.00951

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00332

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00582

Gnomad4 OTH

AF:

0.0455

Alfa

AF:

0.00917

Hom.:

Bravo

AF:

0.0647

TwinsUK

AF:

0.00620

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.175

AC:

658

ESP6500EA

AF:

0.00619

AC:

ExAC

AF:

0.0198

AC:

2394

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.00573

EpiControl

AF:

0.00699

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DMBT1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 05, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.035

.;.;.;.;T;.;T

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.61

T;.;.;T;.;T;T

MetaRNN

Benign

0.0014

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N;N;N;N;N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.67

N;N;N;N;N;N;.

REVEL

Benign

0.089

Sift

Uncertain

0.015

D;D;D;D;D;D;.

Sift4G

Benign

0.071

T;T;D;T;T;D;T

Polyphen

0.57

P;P;P;P;D;P;D

Vest4

0.19

MPC

0.36

ClinPred

0.035

GERP RS

0.97

Varity_R

0.070

gMVP

0.29

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over