Genetic Variant DHX30:p.Ser148Tyr (chr3-47840953-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138615.3(DHX30):c.443C>A(p.Ser148Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S148T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 30)

Consequence

DHX30
NM_138615.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.43

Publications

0 publications found

Variant links:

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)

DHX30 links:

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ACMG classification

Classification was made for transcript

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=0.22916925).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DHX30	NM_138615.3	MANE Select	c.443C>A	p.Ser148Tyr	missense	Exon 7 of 22	NP_619520.1	Q7L2E3-1
DHX30	NM_001330990.2		c.359C>A	p.Ser120Tyr	missense	Exon 8 of 23	NP_001317919.1	H7BXY3
DHX30	NM_014966.4		c.326C>A	p.Ser109Tyr	missense	Exon 8 of 23	NP_055781.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DHX30	ENST00000445061.6	TSL:1 MANE Select	c.443C>A	p.Ser148Tyr	missense	Exon 7 of 22	ENSP00000405620.1	Q7L2E3-1
DHX30	ENST00000395745.6	TSL:1	n.*343C>A		non_coding_transcript_exon	Exon 8 of 23	ENSP00000379094.2	F6R0H4
DHX30	ENST00000395745.6	TSL:1	n.*343C>A		3_prime_UTR	Exon 8 of 23	ENSP00000379094.2	F6R0H4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.051

Eigen

Benign

0.093

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.0068

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.34

PhyloP100

3.4

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.60

REVEL

Benign

0.088

Sift

Uncertain

0.0090

Sift4G

Benign

0.23

Polyphen

0.39

Vest4

0.40

MutPred

0.25

Loss of disorder (P = 0.0221)

MVP

0.29

MPC

1.4

ClinPred

0.39

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.063

gMVP

0.79

Mutation Taster

=70/30

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over