rs1421998947

Variant names:

• chr3-47840961-G-A
• rs1421998947
• NM_138615.3:c.451G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-47840961-G-A
• chr3-47840961-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_138615.3(DHX30):​c.451G>A​(p.Asp151Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000682 in 1,614,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. D151Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: DHX30 NM_138615.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.99
• 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: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHX30	NM_138615.3	c.451G>A	p.Asp151Asn	missense_variant	Exon 7 of 22	ENST00000445061.6	NP_619520.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHX30	ENST00000445061.6	c.451G>A	p.Asp151Asn	missense_variant	Exon 7 of 22	1	NM_138615.3	ENSP00000405620.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152174 Hom.: 0 Cov.: 30

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: 0.0000441

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461890 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152174 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 74334

African (AFR) AF: 0.0000241 AC: 1 AN: 41438

American (AMR) AF: 0.00 AC: 0 AN: 15274

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.049	T;T;T;.;.
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.96	.;D;D;D;D
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.21	T;T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.34	N;.;N;.;.
PhyloP100		6.0
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.75	N;N;.;.;N
REVEL	Benign	0.069
Sift	Uncertain	0.0030	D;D;.;.;D
Sift4G	Benign	0.068	T;T;T;T;T
Polyphen		0.80	P;.;P;B;P
Vest4		0.26
MutPred		0.21		Gain of MoRF binding (P = 0.0377);.;Gain of MoRF binding (P = 0.0377);.;.;
MVP		0.48
MPC		1.1
ClinPred		0.72	D
GERP RS		4.9
Varity_R		0.090
gMVP		0.66
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.26		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.26		Position offset: 5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1421998947; hg19: chr3-47882451;