9-132592859-T-C

Variant names:

• chr9-132592859-T-C
• rs7859473
• NM_022779.9:c.*2007A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_022779.9(DDX31):​c.*2007A>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0261 in 152,224 control chromosomes in the GnomAD database, including 104 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.026 (104 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DDX31 NM_022779.9 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.996
• Publications: 3 publications found

Genes affected

DDX31 (HGNC:16715): (DEAD-box helicase 31) 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 DEAD box protein family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a member of this family. The function of this member has not been determined. Alternative splicing of this gene generates multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0261 (3975/152224) while in subpopulation AFR AF = 0.0248 (1029/41540). AF 95% confidence interval is 0.0235. There are 104 homozygotes in GnomAd4. There are 2139 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 104 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022779.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX31	NM_022779.9	MANE Select	c.*2007A>G		downstream_gene	N/A	NP_073616.7
	DDX31	NM_001322341.2		c.*2007A>G		downstream_gene	N/A	NP_001309270.1
	DDX31	NM_001322343.1		c.*2007A>G		downstream_gene	N/A	NP_001309272.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX31	ENST00000372159.8	TSL:1 MANE Select	c.*2007A>G		downstream_gene	N/A	ENSP00000361232.4
	DDX31	ENST00000372155.2	TSL:2	n.*138A>G		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0261 AC: 3969 AN: 152108 Hom.: 103 Cov.: 32

Gnomad AFR AF: 0.0248

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.00720

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0233

Gnomad OTH AF: 0.0177

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.0261 AC: 3975 AN: 152224 Hom.: 104 Cov.: 32 AF XY: 0.0287 AC XY: 2139 AN XY: 74422

African (AFR) AF: 0.0248 AC: 1029 AN: 41540

American (AMR) AF: 0.00719 AC: 110 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 35 AN: 3470

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5184

South Asian (SAS) AF: 0.00208 AC: 10 AN: 4818

European-Finnish (FIN) AF: 0.103 AC: 1090 AN: 10574

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0233 AC: 1587 AN: 68024

Other (OTH) AF: 0.0194 AC: 41 AN: 2112

Alfa AF: 0.0324 Hom.: 26

Bravo AF: 0.0180

Asia WGS AF: 0.0170 AC: 58 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.6
DANN	Benign	0.48
PhyloP100		-1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7859473; hg19: chr9-135468246;