NM_016222.4:c.*63T>C

Variant names:

• chr5-177511728-A-G
• rs937006672
• NM_016222.4:c.*63T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_016222.4(DDX41):​c.*63T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 1,599,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: DDX41 NM_016222.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.579
• Publications: 1 publications found

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]

DDX41 Gene-Disease associations (from GenCC):

• DDX41-related hematologic malignancy predisposition syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp, ClinGen
• acromesomelic dysplasia

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016222.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX41	NM_016222.4	MANE Select	c.*63T>C		3_prime_UTR	Exon 17 of 17	NP_057306.2
	DDX41	NM_001321732.2		c.*63T>C		3_prime_UTR	Exon 16 of 16	NP_001308661.1	B3KRK2
	DDX41	NM_001321830.2		c.*63T>C		3_prime_UTR	Exon 17 of 17	NP_001308759.1	B3KRK2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX41	ENST00000330503.12	TSL:1 MANE Select	c.*63T>C		3_prime_UTR	Exon 17 of 17	ENSP00000330349.8	Q9UJV9
	DDX41	ENST00000507955.6	TSL:1	n.*1140T>C		non_coding_transcript_exon	Exon 17 of 17	ENSP00000422753.2	A0A499FJW5
	DDX41	ENST00000507955.6	TSL:1	n.*1140T>C		3_prime_UTR	Exon 17 of 17	ENSP00000422753.2	A0A499FJW5

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152180 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.00

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.00000691 AC: 10 AN: 1447698 Hom.: 0 Cov.: 32 AF XY: 0.00000696 AC XY: 5 AN XY: 718218

African (AFR) AF: 0.000180 AC: 6 AN: 33248

American (AMR) AF: 0.0000676 AC: 3 AN: 44362

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25574

East Asian (EAS) AF: 0.00 AC: 0 AN: 39406

South Asian (SAS) AF: 0.00 AC: 0 AN: 85362

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52784

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1101438

Other (OTH) AF: 0.0000167 AC: 1 AN: 59802

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152180 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74356

African (AFR) AF: 0.000217 AC: 9 AN: 41446

American (AMR) AF: 0.0000654 AC: 1 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000159

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.0
DANN	Benign	0.38
PhyloP100		0.58
PromoterAI		0.0014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs937006672; hg19: chr5-176938729;