Variant rs8106337 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_203486.3(DLL3):c.546C>A(p.Ala182=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000384 in 1,302,030 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A182A) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000038 ( 0 hom. )

Consequence

DLL3
NM_203486.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0910

Variant links:

Genes affected

DLL3 (HGNC:2909): (delta like canonical Notch ligand 3) This gene encodes a member of the delta protein ligand family. This family functions as Notch ligands that are characterized by a DSL domain, EGF repeats, and a transmembrane domain. Mutations in this gene cause autosomal recessive spondylocostal dysostosis 1. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

DLL3 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP7

Synonymous conserved (PhyloP=-0.091 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLL3	NM_203486.3 linkuse as main transcript	c.546C>A	p.Ala182=	synonymous_variant	4/9	ENST00000356433.10
DLL3	NM_016941.4 linkuse as main transcript	c.546C>A	p.Ala182=	synonymous_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLL3	ENST00000356433.10 linkuse as main transcript	c.546C>A	p.Ala182=	synonymous_variant	4/9	2	NM_203486.3	P1	Q9NYJ7-2
DLL3	ENST00000205143.4 linkuse as main transcript	c.546C>A	p.Ala182=	synonymous_variant	4/8	1			Q9NYJ7-1
DLL3	ENST00000600437.1 linkuse as main transcript	n.626C>A		non_coding_transcript_exon_variant	4/6	1
DLL3	ENST00000596614.5 linkuse as main transcript	c.409+2279C>A		intron_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000148

AC:

AN:

67630

Hom.:

AF XY:

0.00

AC XY:

AN XY:

39396

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000391

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000384

AC:

AN:

1302030

Hom.:

Cov.:

AF XY:

0.00000156

AC XY:

AN XY:

641342

show subpopulations

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:

0.0000143

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000384

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

5.4

DANN

Benign

0.80

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over