chr10-122572320-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

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

Publications

10 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 3038002.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

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.194C>T	p.Pro65Leu	missense	Exon 5 of 56	NP_001364459.1	Q9UGM3-6
DMBT1	NM_007329.3		c.194C>T	p.Pro65Leu	missense	Exon 5 of 53	NP_015568.2	Q9UGM3-1
DMBT1	NM_001320644.2		c.194C>T	p.Pro65Leu	missense	Exon 5 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.194C>T	p.Pro65Leu	missense	Exon 5 of 56	ENSP00000342210.4	Q9UGM3-6
DMBT1	ENST00000344338.7	TSL:1	c.194C>T	p.Pro65Leu	missense	Exon 5 of 52	ENSP00000343175.3	Q9UGM3-3
DMBT1	ENST00000330163.8	TSL:1	c.194C>T	p.Pro65Leu	missense	Exon 5 of 40	ENSP00000327747.4	Q9UGM3-2

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

GnomAD2 exomes

AF:

0.00143

AC:

356

AN:

249256

AF XY:

0.00133

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 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

African (AFR)

AF:

0.000329

AC:

AN:

33472

American (AMR)

AF:

0.00184

AC:

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

26116

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39686

South Asian (SAS)

AF:

0.0000812

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00113

AC:

AN:

53304

Middle Eastern (MID)

AF:

0.00173

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00238

AC:

2646

AN:

1111310

Other (OTH)

AF:

0.00269

AC:

162

AN:

60320

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

167

334

500

667

834

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

200

300

400

500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00194

AC:

296

AN:

152268

Hom.:

Cov.:

AF XY:

0.00201

AC XY:

150

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.000843

AC:

AN:

41536

American (AMR)

AF:

0.00248

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000208

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00254

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00212

AC:

144

AN:

68034

Other (OTH)

AF:

0.00237

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00218

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

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

DMBT1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.65

CADD

Benign

6.4

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.023

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.00012

LIST_S2

Benign

0.48

M_CAP

Benign

0.00087

MetaRNN

Benign

0.0054

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

PhyloP100

-0.34

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.29

REVEL

Benign

0.011

Sift

Benign

0.17

Sift4G

Benign

0.62

Polyphen

0.19

Vest4

0.062

MVP

0.21

MPC

0.053

ClinPred

0.0034

GERP RS

-2.9

Varity_R

0.021

gMVP

0.22

Mutation Taster

=100/0

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over