17-43484063-G-A

Variant names:

• chr17-43484063-G-A
• rs759644929
• NM_004941.3:c.26G>A

Variant summary

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

The NM_004941.3(DHX8):​c.26G>A​(p.Gly9Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G9V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DHX8 NM_004941.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0650
• Publications: 0 publications found

Genes affected

DHX8 (HGNC:2749): (DEAH-box helicase 8) This gene is a member of the DEAH box polypeptide family. The encoded protein contains the DEAH (Asp-Glu-Ala-His) motif which is characteristic of all DEAH box proteins, and is thought to function as an ATP-dependent RNA helicase that regulates the release of spliced mRNAs from spliceosomes prior to their export from the nucleus. This protein may be required for the replication of human immunodeficiency virus type 1 (HIV-1). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

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=0.08825281).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004941.3. 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
	DHX8	NM_004941.3	MANE Select	c.26G>A	p.Gly9Glu	missense	Exon 1 of 23	NP_004932.1	Q14562
	DHX8	NM_001322221.2		c.26G>A	p.Gly9Glu	missense	Exon 1 of 23	NP_001309150.1
	DHX8	NM_001302623.3		c.26G>A	p.Gly9Glu	missense	Exon 1 of 23	NP_001289552.1	F5H658

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHX8	ENST00000262415.8	TSL:1 MANE Select	c.26G>A	p.Gly9Glu	missense	Exon 1 of 23	ENSP00000262415.2	Q14562
	DHX8	ENST00000958205.1		c.26G>A	p.Gly9Glu	missense	Exon 1 of 24	ENSP00000628264.1
	DHX8	ENST00000958204.1		c.26G>A	p.Gly9Glu	missense	Exon 1 of 23	ENSP00000628263.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461870 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727240

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

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

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112000

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	16
DANN	Benign	0.86
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.065
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.092
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.027	D
Polyphen		0.0	B
Vest4		0.29
MutPred		0.40		Loss of catalytic residue at A8 (P = 0.0094)
MVP		0.093
MPC		0.64
ClinPred		0.25	T
GERP RS		1.3
PromoterAI		0.26	Neutral
Varity_R		0.085
gMVP		0.57
Mutation Taster		=95/5	polymorphism

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: rs759644929; hg19: chr17-41561431;