3-47829038-C-A

Variant names:

• chr3-47829038-C-A
• NM_138615.3:c.270C>A

Variant summary

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

The NM_138615.3(DHX30):​c.270C>A​(p.His90Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,456,944 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DHX30 NM_138615.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0950
• Publications: 0 publications found

Genes affected

DHX30 (HGNC:16716): (DExH-box helicase 30) 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. The family member encoded by this gene is a mitochondrial nucleoid protein that associates with mitochondrial DNA. It has also been identified as a component of a transcriptional repressor complex that functions in retinal development, and it is required to optimize the function of the zinc-finger antiviral protein. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Feb 2013]

DHX30 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with severe motor impairment and absent language

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae)

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=0.17138222).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138615.3. 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
	DHX30	NM_138615.3	MANE Select	c.270C>A	p.His90Gln	missense	Exon 6 of 22	NP_619520.1	Q7L2E3-1
	DHX30	NM_001330990.2		c.186C>A	p.His62Gln	missense	Exon 7 of 23	NP_001317919.1	H7BXY3
	DHX30	NM_014966.4		c.153C>A	p.His51Gln	missense	Exon 7 of 23	NP_055781.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHX30	ENST00000445061.6	TSL:1 MANE Select	c.270C>A	p.His90Gln	missense	Exon 6 of 22	ENSP00000405620.1	Q7L2E3-1
	DHX30	ENST00000395745.6	TSL:1	n.*170C>A		non_coding_transcript_exon	Exon 7 of 23	ENSP00000379094.2	F6R0H4
	DHX30	ENST00000395745.6	TSL:1	n.*170C>A		3_prime_UTR	Exon 7 of 23	ENSP00000379094.2	F6R0H4

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1456944 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 724816

African (AFR) AF: 0.00 AC: 0 AN: 33342

American (AMR) AF: 0.00 AC: 0 AN: 44368

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25980

East Asian (EAS) AF: 0.00 AC: 0 AN: 39490

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85716

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53158

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108954

Other (OTH) AF: 0.00 AC: 0 AN: 60176

GnomAD4 genome Cov.: 27

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Neurodevelopmental disorder with severe motor impairment and absent language (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	17
DANN	Benign	0.92
DEOGEN2	Benign	0.068	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.095
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.086
Sift	Benign	0.30	T
Sift4G	Benign	0.33	T
Polyphen		0.045	B
Vest4		0.39
MutPred		0.33		Gain of MoRF binding (P = 0.1007)
MVP		0.46
MPC		0.95
ClinPred		0.14	T
GERP RS		2.5
Varity_R		0.055
gMVP		0.84
Mutation Taster		=62/38	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

hg19: chr3-47870528;