17-5468744-C-A

Variant names:

• chr17-5468744-C-A
• rs776166919
• NM_020162.4:c.116G>T

Variant summary

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

The NM_020162.4(DHX33):​c.116G>T​(p.Gly39Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,226 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. G39D) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: DHX33 NM_020162.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0700
• Publications: 1 publications found

Genes affected

DHX33 (HGNC:16718): (DEAH-box helicase 33) This gene encodes a member of the DEAD box protein family. The DEAD box proteins are 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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2010]

DHX33-DT (HGNC:52937): (DHX33 divergent transcript)

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=0.102190256).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020162.4. 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
	DHX33	NM_020162.4	MANE Select	c.116G>T	p.Gly39Val	missense	Exon 1 of 12	NP_064547.2
	DHX33	NM_001199699.2		c.-243G>T		5_prime_UTR	Exon 1 of 11	NP_001186628.1	Q9H6R0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHX33	ENST00000225296.8	TSL:1 MANE Select	c.116G>T	p.Gly39Val	missense	Exon 1 of 12	ENSP00000225296.3	Q9H6R0-1
	DHX33	ENST00000572490.1	TSL:1	c.4G>T	p.Ala2Ser	missense	Exon 1 of 11	ENSP00000458925.1	I3L1L6
	DHX33	ENST00000433302.7	TSL:1	c.116G>T	p.Gly39Val	missense	Exon 1 of 8	ENSP00000413779.3	Q05BE5

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152226 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152226 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74364

African (AFR) AF: 0.0000241 AC: 1 AN: 41462

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.0095	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.070
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.037
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.039	D
Polyphen		0.082	B
Vest4		0.18
MutPred		0.36		Gain of sheet (P = 0.0101)
MVP		0.61
MPC		0.34
ClinPred		0.76	D
GERP RS		2.9
PromoterAI		0.096	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.16
gMVP		0.53

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: rs776166919; hg19: chr17-5372064;