chr10-122576477-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001377530.1(DMBT1):c.362G>C(p.Gly121Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
DMBT1
NM_001377530.1 missense
NM_001377530.1 missense
Scores
2
8
8
Clinical Significance
Conservation
PhyloP100: 1.24
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 Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.38604522).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DMBT1 | NM_001377530.1 | c.362G>C | p.Gly121Ala | missense_variant | 7/56 | ENST00000338354.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DMBT1 | ENST00000338354.10 | c.362G>C | p.Gly121Ala | missense_variant | 7/56 | 1 | NM_001377530.1 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152204Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249380Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135280
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GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461688Hom.: 0 Cov.: 33 AF XY: 0.0000110 AC XY: 8AN XY: 727124
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152204Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74354
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 17, 2022 | The c.362G>C (p.G121A) alteration is located in exon 7 (coding exon 7) of the DMBT1 gene. This alteration results from a G to C substitution at nucleotide position 362, causing the glycine (G) at amino acid position 121 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.;.;D;.;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;M;M;M;M;M;M
MutationTaster
Benign
D;D;D;D;N;N;N;N;N;N;N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;D;N;N;D;.
REVEL
Benign
Sift
Uncertain
D;D;D;D;D;D;.
Sift4G
Uncertain
D;D;T;D;D;T;D
Polyphen
D;D;P;D;D;P;D
Vest4
MVP
MPC
0.36
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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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