9-132658497-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_022779.9(DDX31):​c.588+174T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000192 in 521,922 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: DDX31 NM_022779.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX31	NM_022779.9	MANE Select	c.588+174T>A		intron	N/A	NP_073616.7
	DDX31	NM_001322341.2		c.615+174T>A		intron	N/A	NP_001309270.1
	DDX31	NM_001322343.1		c.516+174T>A		intron	N/A	NP_001309272.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX31	ENST00000372159.8	TSL:1 MANE Select	c.588+174T>A		intron	N/A	ENSP00000361232.4	Q9H8H2-5
	DDX31	ENST00000480876.3	TSL:1	c.589-139T>A		intron	N/A	ENSP00000479697.2	Q9H8H2-6
	DDX31	ENST00000893393.1		c.588+174T>A		intron	N/A	ENSP00000563452.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000192 AC: 1 AN: 521922 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 277814

African (AFR) AF: 0.00 AC: 0 AN: 14364

American (AMR) AF: 0.00 AC: 0 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: 0.00 AC: 0 AN: 52594

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

Middle Eastern (MID) AF: 0.000262 AC: 1 AN: 3824

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 313050

Other (OTH) AF: 0.00 AC: 0 AN: 29068

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.2
DANN	Benign	0.45
PhyloP100		-0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;