6-117525394-C-T

Position:

• chr6-117525394-C-T

Variant summary

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

The NM_001366458.2(DCBLD1):​c.545C>T​(p.Ala182Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000146 in 1,365,368 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: DCBLD1 NM_001366458.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.34

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 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	c.545C>T	p.Ala182Val	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.545C>T	p.Ala182Val	missense_variant	5/15	5	NM_001366458.2	ENSP00000342422.6
DCBLD1	ENST00000296955.12	c.545C>T	p.Ala182Val	missense_variant	5/15	1		ENSP00000296955.8
ENSG00000282218	ENST00000467125.1	c.547+41460G>A		intron_variant		2		ENSP00000487717.1
DCBLD1	ENST00000533453.5	n.608+3818C>T		intron_variant		1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000146 AC: 2 AN: 1365368 Hom.: 0 Cov.: 30 AF XY: 0.00000148 AC XY: 1 AN XY: 676090

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: 0.0000201

Gnomad4 NFE exome AF: 9.39e-7

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

Aug 19, 2024

The c.545C>T (p.A182V) alteration is located in exon 5 (coding exon 5) of the DCBLD1 gene. This alteration results from a C to T substitution at nucleotide position 545, causing the alanine (A) at amino acid position 182 to be replaced by a valine (V). 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	0.093
BayesDel_addAF	Benign	-0.017	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	18
DANN	Benign	0.79
DEOGEN2	Benign	0.25	.;T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.80	T;T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.6	L;L
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.0	N;N
REVEL	Benign	0.28
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.020	B;P
Vest4		0.27
MutPred		0.52		Gain of sheet (P = 0.0061);Gain of sheet (P = 0.0061);
MVP		0.80
MPC		0.58
ClinPred		0.76	D
GERP RS		3.5
Varity_R		0.070
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.27		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.27		Position offset: -32

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: chr6-117846557;