11-108679558-T-C

Position:

• chr11-108679558-T-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_004398.4(DDX10):​c.846T>C​(p.Tyr282=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00402 in 1,597,166 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0030 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0041 (18 hom.)
• Consequence: DDX10 NM_004398.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.00004668
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.271

Genes affected

DDX10 (HGNC:2735): (DEAD-box helicase 10) DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein, and it may be involved in ribosome assembly. Fusion of this gene and the nucleoporin gene, NUP98, by inversion 11 (p15q22) chromosome translocation is found in the patients with de novo or therapy-related myeloid malignancies. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 11-108679558-T-C is Benign according to our data. Variant chr11-108679558-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 790363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.271 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX10	NM_004398.4	c.846T>C	p.Tyr282=	splice_region_variant, synonymous_variant	6/18	ENST00000322536.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX10	ENST00000322536.8	c.846T>C	p.Tyr282=	splice_region_variant, synonymous_variant	6/18	1	NM_004398.4	P2

Frequencies

GnomAD3 genomes AF: 0.00297 AC: 452 AN: 152218 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000772

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.0156

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00546

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00429

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00292 AC: 691 AN: 237014 Hom.: 2 AF XY: 0.00292 AC XY: 374 AN XY: 128128

Gnomad AFR exome AF: 0.000942

Gnomad AMR exome AF: 0.000426

Gnomad ASJ exome AF: 0.0111

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000478

Gnomad FIN exome AF: 0.00621

Gnomad NFE exome AF: 0.00362

Gnomad OTH exome AF: 0.00334

GnomAD4 exome AF: 0.00413 AC: 5967 AN: 1444830 Hom.: 18 Cov.: 29 AF XY: 0.00401 AC XY: 2881 AN XY: 718704

Gnomad4 AFR exome AF: 0.000556

Gnomad4 AMR exome AF: 0.000571

Gnomad4 ASJ exome AF: 0.0119

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000481

Gnomad4 FIN exome AF: 0.00527

Gnomad4 NFE exome AF: 0.00457

Gnomad4 OTH exome AF: 0.00412

GnomAD4 genome AF: 0.00297 AC: 452 AN: 152336 Hom.: 4 Cov.: 32 AF XY: 0.00278 AC XY: 207 AN XY: 74498

Gnomad4 AFR AF: 0.000770

Gnomad4 AMR AF: 0.000457

Gnomad4 ASJ AF: 0.0156

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00546

Gnomad4 NFE AF: 0.00429

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00350 Hom.: 2

Bravo AF: 0.00255

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00273

EpiControl AF: 0.00362

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2023	DDX10: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 30, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	3.9
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000047
dbscSNV1_RF	Benign	0.0
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

Other links and lift over

dbSNP: rs61751526; hg19: chr11-108550285;