rs772366722

Variant names:

• chr17-43484041-G-A
• rs772366722
• NM_004941.3:c.4G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-43484041-G-A
• chr17-43484041-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004941.3(DHX8):​c.4G>A​(p.Ala2Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,718 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: 0.0000014 (0 hom.)
• Consequence: DHX8 NM_004941.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.35

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28183445).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHX8	NM_004941.3	c.4G>A	p.Ala2Thr	missense_variant	Exon 1 of 23	ENST00000262415.8	NP_004932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHX8	ENST00000262415.8	c.4G>A	p.Ala2Thr	missense_variant	Exon 1 of 23	1	NM_004941.3	ENSP00000262415.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250670 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135602

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461718 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727150

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0086	T;T
Eigen	Benign	-0.13
Eigen_PC	Benign	0.015
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.28	T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.0	.;N
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.18	N;N
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.45	B;B
Vest4		0.48
MutPred		0.35		Gain of glycosylation at A2 (P = 0.0085);Gain of glycosylation at A2 (P = 0.0085);
MVP		0.34
MPC		0.61
ClinPred		0.63	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.19
gMVP		0.61

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

LitVar

Other links and lift over

dbSNP: rs772366722; hg19: chr17-41561409;