9-132658497-A-C

Variant names:

• chr9-132658497-A-C
• rs17149424
• NM_022779.9:c.588+174T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0779 is higher than 0.05.

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.588+174T>G		intron	N/A	NP_073616.7
	DDX31	NM_001322341.2		c.615+174T>G		intron	N/A	NP_001309270.1
	DDX31	NM_001322343.1		c.516+174T>G		intron	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.588+174T>G		intron	N/A	ENSP00000361232.4
	DDX31	ENST00000480876.3	TSL:1	c.589-139T>G		intron	N/A	ENSP00000479697.2
	DDX31	ENST00000310532.7	TSL:2	c.588+174T>G		intron	N/A	ENSP00000310539.2

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

African (AFR) AF: 0.0820 AC: 1178 AN: 14364

American (AMR) AF: 0.00389 AC: 104 AN: 26746

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16516

East Asian (EAS) AF: 0.00 AC: 0 AN: 31846

South Asian (SAS) AF: 0.000152 AC: 8 AN: 52594

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33914

Middle Eastern (MID) AF: 0.00235 AC: 9 AN: 3824

European-Non Finnish (NFE) AF: 0.000115 AC: 36 AN: 313050

Other (OTH) AF: 0.00705 AC: 205 AN: 29068

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

African (AFR) AF: 0.0801 AC: 3326 AN: 41506

American (AMR) AF: 0.00700 AC: 107 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 67994

Other (OTH) AF: 0.0137 AC: 29 AN: 2116

Alfa AF: 0.0148 Hom.: 23

Bravo AF: 0.0266

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.39
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17149424; hg19: chr9-135533884;