NM_007242.7:c.1250A>G

Variant names:

• chr16-70333031-A-G
• rs761158066
• NM_007242.7:c.1250A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007242.7(DDX19B):​c.1250A>G​(p.Asn417Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: DDX19B NM_007242.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.91
• Publications: 1 publications found

Genes affected

DDX19B (HGNC:2742): (DEAD-box helicase 19B) 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, which exhibits RNA-dependent ATPase and ATP-dependent RNA-unwinding activities. This protein is recruited to the cytoplasmic fibrils of the nuclear pore complex, where it participates in the export of mRNA from the nucleus. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ENSG00000260537 (HGNC:):

DDX19A-DT (HGNC:55349): (DDX19A divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09514359).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007242.7. 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
	DDX19B	NM_007242.7	MANE Select	c.1250A>G	p.Asn417Ser	missense	Exon 11 of 12	NP_009173.1	Q9UMR2-1
	DDX19B	NM_001363938.1		c.1265A>G	p.Asn422Ser	missense	Exon 11 of 12	NP_001350867.1	H3BQK0
	DDX19B	NM_001257172.2		c.1172A>G	p.Asn391Ser	missense	Exon 10 of 11	NP_001244101.1	Q9UMR2-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX19B	ENST00000288071.11	TSL:1 MANE Select	c.1250A>G	p.Asn417Ser	missense	Exon 11 of 12	ENSP00000288071.7	Q9UMR2-1
	DDX19B	ENST00000355992.7	TSL:1	c.1157A>G	p.Asn386Ser	missense	Exon 10 of 11	ENSP00000348271.3	Q9UMR2-2
	DDX19B	ENST00000393657.6	TSL:1	c.923A>G	p.Asn308Ser	missense	Exon 9 of 10	ENSP00000377267.2	Q9UMR2-3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000279 AC: 7 AN: 250962 AF XY: 0.0000295

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000203

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461726 Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4 AN XY: 727148

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.000157 AC: 7 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111902

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 31

ExAC AF: 0.0000330 AC: 4

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
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.042
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	-0.47	N
PhyloP100		6.9
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.097
Sift	Benign	0.20	T
Sift4G	Benign	0.37	T
Polyphen		0.0070	B
Vest4		0.37
MutPred		0.35		Gain of phosphorylation at N417 (P = 0.0571)
MVP		0.18
MPC		1.3
ClinPred		0.090	T
GERP RS		4.0
Varity_R		0.18
gMVP		0.75

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: rs761158066; hg19: chr16-70366934;