Variant 10-122570194-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000338354.10(DMBT1):c.124C>A(p.Pro42Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.697 in 1,556,636 control chromosomes in the GnomAD database, including 383,520 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.69 ( 36132 hom., cov: 33)

Exomes 𝑓: 0.70 ( 347388 hom. )

Consequence

DMBT1
ENST00000338354.10 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.15

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.2438222E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.755 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.124C>A	p.Pro42Thr	missense_variant	3/56	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.124C>A	p.Pro42Thr	missense_variant	3/56	1	NM_001377530.1	ENSP00000342210	P4	Q9UGM3-6

Frequencies

GnomAD3 genomes

AF:

0.688

AC:

104427

AN:

151890

Hom.:

36103

Cov.:

show subpopulations

Gnomad AFR

AF:

0.633

Gnomad AMI

AF:

0.734

Gnomad AMR

AF:

0.757

Gnomad ASJ

AF:

0.663

Gnomad EAS

AF:

0.776

Gnomad SAS

AF:

0.749

Gnomad FIN

AF:

0.747

Gnomad MID

AF:

0.684

Gnomad NFE

AF:

0.685

Gnomad OTH

AF:

0.685

GnomAD3 exomes

AF:

0.724

AC:

180311

AN:

249142

Hom.:

66010

AF XY:

0.722

AC XY:

97598

AN XY:

135152

show subpopulations

Gnomad AFR exome

AF:

0.623

Gnomad AMR exome

AF:

0.847

Gnomad ASJ exome

AF:

0.649

Gnomad EAS exome

AF:

0.790

Gnomad SAS exome

AF:

0.742

Gnomad FIN exome

AF:

0.742

Gnomad NFE exome

AF:

0.688

Gnomad OTH exome

AF:

0.717

GnomAD4 exome

AF:

0.698

AC:

979787

AN:

1404628

Hom.:

347388

Cov.:

AF XY:

0.699

AC XY:

490074

AN XY:

701346

show subpopulations

Gnomad4 AFR exome

AF:

0.619

Gnomad4 AMR exome

AF:

0.836

Gnomad4 ASJ exome

AF:

0.652

Gnomad4 EAS exome

AF:

0.805

Gnomad4 SAS exome

AF:

0.737

Gnomad4 FIN exome

AF:

0.737

Gnomad4 NFE exome

AF:

0.686

Gnomad4 OTH exome

AF:

0.694

GnomAD4 genome

AF:

0.687

AC:

104499

AN:

152008

Hom.:

36132

Cov.:

AF XY:

0.693

AC XY:

51509

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.633

Gnomad4 AMR

AF:

0.757

Gnomad4 ASJ

AF:

0.663

Gnomad4 EAS

AF:

0.775

Gnomad4 SAS

AF:

0.750

Gnomad4 FIN

AF:

0.747

Gnomad4 NFE

AF:

0.685

Gnomad4 OTH

AF:

0.688

Alfa

AF:

0.688

Hom.:

27467

Bravo

AF:

0.689

TwinsUK

AF:

0.682

AC:

2530

ALSPAC

AF:

0.673

AC:

2594

ESP6500AA

AF:

0.642

AC:

2407

ESP6500EA

AF:

0.689

AC:

5666

ExAC

AF:

0.716

AC:

86478

Asia WGS

AF:

0.749

AC:

2606

AN:

3478

EpiCase

AF:

0.690

EpiControl

AF:

0.696

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.0010

DANN

Benign

0.40

DEOGEN2

Benign

0.020

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

Eigen

Benign

-2.7

Eigen_PC

Benign

-2.8

FATHMM_MKL

Benign

0.00039

LIST_S2

Benign

0.28

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

MetaRNN

Benign

0.0000012

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

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

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

MutationTaster

Benign

1.0

P;P;P;P;P;P;P;P;P;P;P;P;P;P

PrimateAI

Benign

0.22

PROVEAN

Benign

0.51

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

REVEL

Benign

0.0080

Sift

Benign

0.83

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

Sift4G

Benign

0.061

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

Polyphen

0.015

B;B;B;B;B;B;B

Vest4

0.019

MPC

0.057

ClinPred

0.00026

GERP RS

-3.0

Varity_R

0.024

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over