Variant 6-117519881-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001366458.2(DCBLD1):c.391C>T(p.Arg131Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000204 in 1,613,960 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

DCBLD1
NM_001366458.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.81

Variant links:

Genes affected

DCBLD1 (HGNC:21479): (discoidin, CUB and LCCL domain containing 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

DCBLD1 links:

ENSG00000282218 (HGNC:):

ENSG00000282218 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCBLD1	NM_001366458.2 linkuse as main transcript	c.391C>T	p.Arg131Cys	missense_variant	3/15	ENST00000338728.10	NP_001353387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DCBLD1	ENST00000338728.10 linkuse as main transcript	c.391C>T	p.Arg131Cys	missense_variant	3/15	5	NM_001366458.2	ENSP00000342422.6	Q8N8Z6-1
DCBLD1	ENST00000296955.12 linkuse as main transcript	c.391C>T	p.Arg131Cys	missense_variant	3/15	1		ENSP00000296955.8	Q8N8Z6-2
ENSG00000282218	ENST00000467125.1 linkuse as main transcript	c.547+46973G>A		intron_variant		2		ENSP00000487717.1	A0A0J9YVX5
DCBLD1	ENST00000533453.5 linkuse as main transcript	n.487C>T		non_coding_transcript_exon_variant	2/11	1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251376

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000219

AC:

AN:

1461812

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000252

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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 22, 2024

The c.391C>T (p.R131C) alteration is located in exon 3 (coding exon 3) of the DCBLD1 gene. This alteration results from a C to T substitution at nucleotide position 391, causing the arginine (R) at amino acid position 131 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.37

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.26

.;T

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.044

MetaRNN

Uncertain

0.62

D;D

MetaSVM

Benign

-0.71

MutationAssessor

Pathogenic

3.3

M;M

PrimateAI

Benign

0.33

PROVEAN

Benign

-2.4

N;N

REVEL

Benign

0.26

Sift

Uncertain

0.027

D;D

Sift4G

Uncertain

0.018

D;D

Polyphen

1.0

D;D

Vest4

0.48

MutPred

0.56

Loss of methylation at R131 (P = 0.0305);Loss of methylation at R131 (P = 0.0305);

MVP

0.44

MPC

0.82

ClinPred

0.87

GERP RS

4.7

Varity_R

0.22

gMVP

0.56

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over