6-117525405-T-C

Position:

• chr6-117525405-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001366458.2(DCBLD1):​c.556T>C​(p.Ser186Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DCBLD1 NM_001366458.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.84

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]

ENSG00000282218 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.838

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCBLD1	NM_001366458.2	c.556T>C	p.Ser186Pro	missense_variant	5/15	ENST00000338728.10	NP_001353387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCBLD1	ENST00000338728.10	c.556T>C	p.Ser186Pro	missense_variant	5/15	5	NM_001366458.2	ENSP00000342422.6
DCBLD1	ENST00000296955.12	c.556T>C	p.Ser186Pro	missense_variant	5/15	1		ENSP00000296955.8
ENSG00000282218	ENST00000467125.1	c.547+41449A>G		intron_variant		2		ENSP00000487717.1
DCBLD1	ENST00000533453.5	n.608+3829T>C		intron_variant		1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1364512 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 675700

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 17, 2024

The c.556T>C (p.S186P) alteration is located in exon 5 (coding exon 5) of the DCBLD1 gene. This alteration results from a T to C substitution at nucleotide position 556, causing the serine (S) at amino acid position 186 to be replaced by a proline (P). 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	Pathogenic	0.72
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.68	.;D
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.80	T;T
M_CAP	Benign	0.051	D
MetaRNN	Pathogenic	0.84	D;D
MetaSVM	Uncertain	0.082	D
MutationAssessor	Uncertain	2.8	M;M
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.6	D;D
REVEL	Pathogenic	0.74
Sift	Uncertain	0.016	D;D
Sift4G	Uncertain	0.029	D;T
Polyphen		1.0	D;D
Vest4		0.79
MutPred		0.56		Loss of glycosylation at S186 (P = 0.0115);Loss of glycosylation at S186 (P = 0.0115);
MVP		0.96
MPC		0.29
ClinPred		0.97	D
GERP RS		4.2
Varity_R		0.65
gMVP		0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-117846568;