Genetic Variant NM_001377530.1:c.124C>T (chr10-122570194-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001377530.1(DMBT1):c.124C>T(p.Pro42Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DMBT1
NM_001377530.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.15

Publications

31 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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.030908823).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMBT1	NM_001377530.1 link	c.124C>T	p.Pro42Ser	missense_variant	Exon 3 of 56	ENST00000338354.10	NP_001364459.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMBT1	ENST00000338354.10 link	c.124C>T	p.Pro42Ser	missense_variant	Exon 3 of 56	1	NM_001377530.1	ENSP00000342210.4		Q9UGM3-6

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151946

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1431550

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

713696

African (AFR)

AF:

0.00

AC:

AN:

32862

American (AMR)

AF:

0.00

AC:

AN:

44646

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25948

East Asian (EAS)

AF:

0.00

AC:

AN:

39520

South Asian (SAS)

AF:

0.00

AC:

AN:

85592

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53348

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5714

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1084588

Other (OTH)

AF:

0.00

AC:

AN:

59332

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

151946

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74206

African (AFR)

AF:

0.00

AC:

AN:

41342

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67960

Other (OTH)

AF:

0.00

AC:

AN:

2092

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.0010

(source)

DANN

Benign

0.41

DEOGEN2

Benign

0.020

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

Eigen

Benign

-2.7

Eigen_PC

Benign

-2.8

FATHMM_MKL

Benign

0.0018

LIST_S2

Benign

0.30

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

M_CAP

Benign

0.0012

MetaRNN

Benign

0.031

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.34

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

PhyloP100

-3.1

PrimateAI

Benign

0.21

PROVEAN

Benign

0.45

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

REVEL

Benign

0.010

Sift

Benign

0.80

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

Sift4G

Benign

0.073

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

Polyphen

0.015

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

Vest4

0.031

MutPred

0.24

Gain of glycosylation at P42 (P = 0.013);Gain of glycosylation at P42 (P = 0.013);Gain of glycosylation at P42 (P = 0.013);Gain of glycosylation at P42 (P = 0.013);Gain of glycosylation at P42 (P = 0.013);Gain of glycosylation at P42 (P = 0.013);Gain of glycosylation at P42 (P = 0.013);

MVP

0.12

MPC

0.053

ClinPred

0.089

GERP RS

-3.0

Varity_R

0.016

gMVP

0.32

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over