9-132658497-A-C

Position:

• chr9-132658497-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022779.9(DDX31):​c.588+174T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00744 in 674,100 control chromosomes in the GnomAD database, including 185 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 0.023 (136 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (49 hom.)
• Consequence: DDX31 NM_022779.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX31	NM_022779.9	c.588+174T>G		intron_variant		ENST00000372159.8	NP_073616.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX31	ENST00000372159.8	c.588+174T>G		intron_variant		1	NM_022779.9	ENSP00000361232	P1
DDX31	ENST00000480876.3	c.589-139T>G		intron_variant		1		ENSP00000479697
DDX31	ENST00000310532.7	c.588+174T>G		intron_variant		2		ENSP00000310539

Frequencies

GnomAD3 genomes AF: 0.0228 AC: 3469 AN: 152060 Hom.: 135 Cov.: 32

Gnomad AFR AF: 0.0802

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00701

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.0138

GnomAD4 exome AF: 0.00295 AC: 1540 AN: 521922 Hom.: 49 AF XY: 0.00239 AC XY: 665 AN XY: 277814

Gnomad4 AFR exome AF: 0.0820

Gnomad4 AMR exome AF: 0.00389

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000152

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000115

Gnomad4 OTH exome AF: 0.00705

GnomAD4 genome AF: 0.0228 AC: 3477 AN: 152178 Hom.: 136 Cov.: 32 AF XY: 0.0220 AC XY: 1639 AN XY: 74406

Gnomad4 AFR AF: 0.0801

Gnomad4 AMR AF: 0.00700

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.0196 Hom.: 13

Bravo AF: 0.0266

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17149424; hg19: chr9-135533884;