Variant 10-122572320-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001377530.1(DMBT1):c.194C>T(p.Pro65Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00205 in 1,613,176 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0019 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0021 ( 5 hom. )

Consequence

DMBT1
NM_001377530.1 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.344

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00543952).

BP6

Variant 10-122572320-C-T is Benign according to our data. Variant chr10-122572320-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3038002.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMBT1	NM_001377530.1 linkuse as main transcript	c.194C>T	p.Pro65Leu	missense_variant	5/56	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.194C>T	p.Pro65Leu	missense_variant	5/56	1	NM_001377530.1	ENSP00000342210.4		Q9UGM3-6

Frequencies

GnomAD3 genomes

AF:

0.00195

AC:

296

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000845

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00254

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00212

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00143

AC:

356

AN:

249256

Hom.:

AF XY:

0.00133

AC XY:

180

AN XY:

135216

show subpopulations

Gnomad AFR exome

AF:

0.000517

Gnomad AMR exome

AF:

0.00165

Gnomad ASJ exome

AF:

0.00109

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00158

Gnomad NFE exome

AF:

0.00206

Gnomad OTH exome

AF:

0.00149

GnomAD4 exome

AF:

0.00206

AC:

3010

AN:

1460908

Hom.:

Cov.:

AF XY:

0.00203

AC XY:

1473

AN XY:

726746

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.00184

Gnomad4 ASJ exome

AF:

0.00115

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00113

Gnomad4 NFE exome

AF:

0.00238

Gnomad4 OTH exome

AF:

0.00269

GnomAD4 genome

AF:

0.00194

AC:

296

AN:

152268

Hom.:

Cov.:

AF XY:

0.00201

AC XY:

150

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000843

Gnomad4 AMR

AF:

0.00248

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00254

Gnomad4 NFE

AF:

0.00212

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00234

Hom.:

Bravo

AF:

0.00202

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.000525

AC:

ESP6500EA

AF:

0.00303

AC:

ExAC

AF:

0.00135

AC:

163

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00234

EpiControl

AF:

0.00249

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DMBT1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 31, 2022

This variant is classified as likely 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

0.11

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.65

CADD

Benign

6.4

DANN

Benign

0.89

DEOGEN2

Benign

0.023

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

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.00012

LIST_S2

Benign

0.48

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

M_CAP

Benign

0.00087

MetaRNN

Benign

0.0054

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

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

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.29

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

REVEL

Benign

0.011

Sift

Benign

0.17

T;T;D;T;T;D;.

Sift4G

Benign

0.62

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

Polyphen

0.19

B;B;B;B;P;B;P

Vest4

0.062

MVP

0.21

MPC

0.053

ClinPred

0.0034

GERP RS

-2.9

Varity_R

0.021

gMVP

0.22

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

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