10-122570911-C-T

Variant names:

• chr10-122570911-C-T
• rs3013236
• NM_001377530.1:c.161C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001377530.1(DMBT1):​c.161C>T​(p.Ser54Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 1,610,984 control chromosomes in the GnomAD database, including 394,785 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.69 (36157 hom., cov: 32)
  • Exomes 𝑓: 0.70 (358628 hom.)
• Consequence: DMBT1 NM_001377530.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.77
• Publications: 28 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.0714485E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMBT1	NM_001377530.1	MANE Select	c.161C>T	p.Ser54Leu	missense	Exon 4 of 56	NP_001364459.1
	DMBT1	NM_007329.3		c.161C>T	p.Ser54Leu	missense	Exon 4 of 53	NP_015568.2
	DMBT1	NM_001320644.2		c.161C>T	p.Ser54Leu	missense	Exon 4 of 53	NP_001307573.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMBT1	ENST00000338354.10	TSL:1 MANE Select	c.161C>T	p.Ser54Leu	missense	Exon 4 of 56	ENSP00000342210.4
	DMBT1	ENST00000344338.7	TSL:1	c.161C>T	p.Ser54Leu	missense	Exon 4 of 52	ENSP00000343175.3
	DMBT1	ENST00000330163.8	TSL:1	c.161C>T	p.Ser54Leu	missense	Exon 4 of 40	ENSP00000327747.4

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104469 AN: 151900 Hom.: 36128 Cov.: 32

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.736

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.749

Gnomad FIN AF: 0.748

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.684

GnomAD2 exomes AF: 0.724 AC: 180307 AN: 249170 AF XY: 0.722

Gnomad AFR exome AF: 0.623

Gnomad AMR exome AF: 0.847

Gnomad ASJ exome AF: 0.649

Gnomad EAS exome AF: 0.788

Gnomad FIN exome AF: 0.742

Gnomad NFE exome AF: 0.688

Gnomad OTH exome AF: 0.716

GnomAD4 exome AF: 0.700 AC: 1020634 AN: 1458966 Hom.: 358628 Cov.: 58 AF XY: 0.700 AC XY: 508481 AN XY: 725986

African (AFR) AF: 0.623 AC: 20847 AN: 33440

American (AMR) AF: 0.836 AC: 37373 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 17053 AN: 26106

East Asian (EAS) AF: 0.803 AC: 31865 AN: 39694

South Asian (SAS) AF: 0.738 AC: 63588 AN: 86184

European-Finnish (FIN) AF: 0.737 AC: 39333 AN: 53394

Middle Eastern (MID) AF: 0.696 AC: 4011 AN: 5764

European-Non Finnish (NFE) AF: 0.689 AC: 764678 AN: 1109412

Other (OTH) AF: 0.695 AC: 41886 AN: 60254

GnomAD4 genome AF: 0.688 AC: 104541 AN: 152018 Hom.: 36157 Cov.: 32 AF XY: 0.694 AC XY: 51527 AN XY: 74294

African (AFR) AF: 0.633 AC: 26250 AN: 41450

American (AMR) AF: 0.758 AC: 11585 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 2301 AN: 3468

East Asian (EAS) AF: 0.774 AC: 3995 AN: 5164

South Asian (SAS) AF: 0.750 AC: 3608 AN: 4810

European-Finnish (FIN) AF: 0.748 AC: 7897 AN: 10560

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.685 AC: 46586 AN: 67964

Other (OTH) AF: 0.688 AC: 1451 AN: 2110

Alfa AF: 0.698 Hom.: 65074

Bravo AF: 0.689

TwinsUK AF: 0.685 AC: 2541

ALSPAC AF: 0.674 AC: 2599

ESP6500AA AF: 0.642 AC: 2434

ESP6500EA AF: 0.690 AC: 5677

ExAC AF: 0.716 AC: 86487

Asia WGS AF: 0.748 AC: 2602 AN: 3478

EpiCase AF: 0.690

EpiControl AF: 0.696

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.087
DANN	Benign	0.86
DEOGEN2	Benign	0.020	T
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.0024	N
LIST_S2	Benign	0.36	T
MetaRNN	Benign	0.0000011	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.34	N
PhyloP100		-2.8
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.0040
Sift	Benign	0.74	T
Sift4G	Benign	0.34	T
Polyphen		0.091	B
Vest4		0.071
MPC		0.048
ClinPred		0.00014	T
GERP RS		-3.1
Varity_R		0.020
gMVP		0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3013236; hg19: chr10-124330427; COSMIC: COSV57547585;