19-47352883-G-C

Variant names:

• chr19-47352883-G-C
• rs1064202
• NM_014681.6:c.-148G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014681.6(DHX34):​c.-148G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 1,428,140 control chromosomes in the GnomAD database, including 23,519 homozygotes. 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: 𝑓 0.24 (6668 hom., cov: 32)
  • Exomes 𝑓: 0.13 (16851 hom.)
• Consequence: DHX34 NM_014681.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 6 publications found

Genes affected

DHX34 (HGNC:16719): (DExH-box helicase 34) 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. It is mapped to the glioma 19q tumor suppressor region and is a tumor suppressor candidate gene. [provided by RefSeq, Jul 2008]

DHX34 Gene-Disease associations (from GenCC):

• intellectual disability

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014681.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHX34	NM_014681.6	MANE Select	c.-148G>C		5_prime_UTR	Exon 2 of 17	NP_055496.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHX34	ENST00000328771.9	TSL:5 MANE Select	c.-148G>C		5_prime_UTR	Exon 2 of 17	ENSP00000331907.4
	DHX34	ENST00000718251.1		n.171G>C		non_coding_transcript_exon	Exon 2 of 14
	DHX34	ENST00000718252.1		c.-148G>C		5_prime_UTR	Exon 2 of 17	ENSP00000520696.1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36643 AN: 151922 Hom.: 6657 Cov.: 32

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.223

GnomAD4 exome AF: 0.132 AC: 168114 AN: 1276100 Hom.: 16851 Cov.: 27 AF XY: 0.135 AC XY: 83367 AN XY: 619260

African (AFR) AF: 0.513 AC: 14427 AN: 28104

American (AMR) AF: 0.206 AC: 4132 AN: 20014

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 2800 AN: 18892

East Asian (EAS) AF: 0.433 AC: 15051 AN: 34762

South Asian (SAS) AF: 0.294 AC: 17970 AN: 61128

European-Finnish (FIN) AF: 0.130 AC: 4404 AN: 33804

Middle Eastern (MID) AF: 0.187 AC: 692 AN: 3696

European-Non Finnish (NFE) AF: 0.0976 AC: 99782 AN: 1022648

Other (OTH) AF: 0.167 AC: 8856 AN: 53052

GnomAD4 genome AF: 0.241 AC: 36690 AN: 152040 Hom.: 6668 Cov.: 32 AF XY: 0.243 AC XY: 18089 AN XY: 74332

African (AFR) AF: 0.492 AC: 20390 AN: 41428

American (AMR) AF: 0.195 AC: 2977 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 518 AN: 3464

East Asian (EAS) AF: 0.451 AC: 2328 AN: 5160

South Asian (SAS) AF: 0.314 AC: 1515 AN: 4820

European-Finnish (FIN) AF: 0.137 AC: 1449 AN: 10580

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6834 AN: 67992

Other (OTH) AF: 0.221 AC: 467 AN: 2112

Alfa AF: 0.115 Hom.: 912

Bravo AF: 0.261

Asia WGS AF: 0.347 AC: 1206 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.089
DANN	Benign	0.42
PhyloP100		-1.1
Mutation Taster		=300/0	polymorphism (auto)

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: rs1064202; hg19: chr19-47856140; COSMIC: COSV60896327;