NM_004941.3:c.322C>A

Variant names:

• chr17-43491179-C-A
• NM_004941.3:c.322C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004941.3(DHX8):​c.322C>A​(p.Pro108Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000721 in 1,387,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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: 7.2e-7 (0 hom.)
• Consequence: DHX8 NM_004941.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.43

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09916183).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHX8	NM_004941.3	c.322C>A	p.Pro108Thr	missense_variant	Exon 4 of 23	ENST00000262415.8	NP_004932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHX8	ENST00000262415.8	c.322C>A	p.Pro108Thr	missense_variant	Exon 4 of 23	1	NM_004941.3	ENSP00000262415.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.21e-7 AC: 1 AN: 1387748 Hom.: 0 Cov.: 28 AF XY: 0.00000145 AC XY: 1 AN XY: 690006

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.30e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.0096	T;T
Eigen	Benign	0.087
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.85	D;D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.099	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.9	.;L
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.38	N;N
REVEL	Benign	0.21
Sift	Benign	0.51	T;T
Sift4G	Benign	0.35	T;T
Polyphen		0.24	B;B
Vest4		0.21
MutPred		0.15		Gain of phosphorylation at P108 (P = 0.0323);Gain of phosphorylation at P108 (P = 0.0323);
MVP		0.38
MPC		0.55
ClinPred		0.58	D
GERP RS		6.0
Varity_R		0.14
gMVP		0.28

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-41568547;