rs746693911

chr5-177513020-T-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_016222.4(DDX41):c.1293A>C(p.Thr431=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0013 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DDX41 NM_016222.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.19

Genes affected

DDX41 (HGNC:18674): (DEAD-box helicase 41) 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 the DEAD box protein family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. The protein encoded by this gene is a member of the DEAD box protein family and interacts with several spliceosomal proteins. In addition, the encoded protein may recognize the bacterial second messengers cyclic di-GMP and cyclic di-AMP, resulting in the induction of genes involved in the innate immune response. [provided by RefSeq, Jan 2017]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 5-177513020-T-G is Benign according to our data. Variant chr5-177513020-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 210842.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.19 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX41	NM_016222.4	c.1293A>C	p.Thr431=	synonymous_variant	12/17	ENST00000330503.12
DDX41	NM_001321732.2	c.915A>C	p.Thr305=	synonymous_variant	11/16
DDX41	NM_001321830.2	c.915A>C	p.Thr305=	synonymous_variant	12/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX41	ENST00000330503.12	c.1293A>C	p.Thr431=	synonymous_variant	12/17	1	NM_016222.4	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 8 AN: 151266 Hom.: 0 Cov.: 33 FAILED QC

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000658

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: 0.0000887

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00135 AC: 1935 AN: 1436040 Hom.: 0 Cov.: 34 AF XY: 0.00156 AC XY: 1111 AN XY: 712510

Gnomad4 AFR exome AF: 0.00146

Gnomad4 AMR exome AF: 0.00338

Gnomad4 ASJ exome AF: 0.00158

Gnomad4 EAS exome AF: 0.00439

Gnomad4 SAS exome AF: 0.00144

Gnomad4 FIN exome AF: 0.00466

Gnomad4 NFE exome AF: 0.000987

Gnomad4 OTH exome AF: 0.00140

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000529 AC: 8 AN: 151370 Hom.: 0 Cov.: 33 AF XY: 0.0000406 AC XY: 3 AN XY: 73906

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.0000657

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000887

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00256 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jul 24, 2015

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.42
Dann	Benign	0.65

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

Other links and lift over

dbSNP: rs746693911; hg19: chr5-176940021;