chr10-122579701-C-T
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_001377530.1(DMBT1):c.803C>T(p.Ala268Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00217 in 1,613,872 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0018 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0022 ( 10 hom. )
Consequence
DMBT1
NM_001377530.1 missense
NM_001377530.1 missense
Scores
4
8
5
Clinical Significance
Conservation
PhyloP100: 3.04
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.007470429).
BP6
Variant 10-122579701-C-T is Benign according to our data. Variant chr10-122579701-C-T is described in ClinVar as [Benign]. Clinvar id is 3034279.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAdExome4 at 10 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DMBT1 | NM_001377530.1 | c.803C>T | p.Ala268Val | missense_variant | 10/56 | ENST00000338354.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DMBT1 | ENST00000338354.10 | c.803C>T | p.Ala268Val | missense_variant | 10/56 | 1 | NM_001377530.1 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00183 AC: 279AN: 152180Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00193 AC: 480AN: 249174Hom.: 1 AF XY: 0.00189 AC XY: 255AN XY: 135160
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GnomAD4 exome AF: 0.00221 AC: 3225AN: 1461574Hom.: 10 Cov.: 34 AF XY: 0.00209 AC XY: 1521AN XY: 727072
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GnomAD4 genome AF: 0.00183 AC: 279AN: 152298Hom.: 1 Cov.: 32 AF XY: 0.00177 AC XY: 132AN XY: 74468
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
DMBT1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 24, 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Pathogenic
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.;.;D;.;D;D
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
H;H;H;H;H;H;H
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;D;N;N;D;.
REVEL
Uncertain
Sift
Pathogenic
D;D;D;D;D;D;.
Sift4G
Uncertain
D;T;T;T;D;T;D
Polyphen
D;D;D;D;D;D;D
Vest4
MVP
MPC
0.35
ClinPred
T
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at