Variant 6-30654876-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_003587.5(DHX16):c.2827A>G(p.Ile943Val) 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 1,458,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

DHX16
NM_003587.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.54

Variant links:

Genes affected

DHX16 (HGNC:2739): (DEAH-box helicase 16) 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 family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein, which is a functional homolog of fission yeast Prp8 protein involved in cell cycle progression. This gene is mapped to the MHC region on chromosome 6p21.3, a region where many malignant, genetic and autoimmune disease genes are linked. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2018]

DHX16 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), DHX16. . Gene score misZ 3.0787 (greater than the threshold 3.09). Trascript score misZ 4.2489 (greater than threshold 3.09). GenCC has associacion of gene with neuromuscular disease and ocular or auditory anomalies with or without seizures.

BP4

Computational evidence support a benign effect (MetaRNN=0.21392158).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHX16	NM_003587.5 linkuse as main transcript	c.2827A>G	p.Ile943Val	missense_variant	19/20	ENST00000376442.8	NP_003578.2	O60231Q5SQH4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHX16	ENST00000376442.8 linkuse as main transcript	c.2827A>G	p.Ile943Val	missense_variant	19/20	1	NM_003587.5	ENSP00000365625.3		O60231
DHX16	ENST00000376437.9 linkuse as main transcript	c.1384A>G	p.Ile462Val	missense_variant	11/12	1		ENSP00000365620.5		Q5SQH5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000411

AC:

AN:

243136

Hom.:

AF XY:

0.00000754

AC XY:

AN XY:

132672

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000924

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458672

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725548

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Neuromuscular disease and ocular or auditory anomalies with or without seizures

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

Mar 26, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.013

.;T

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.016

FATHMM_MKL

Uncertain

0.79

M_CAP

Benign

0.0086

MetaRNN

Benign

0.21

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.5

.;L

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.64

N;N

REVEL

Benign

0.073

Sift

Benign

0.13

T;T

Sift4G

Benign

0.14

T;T

Polyphen

0.0010

B;B

Vest4

0.22

MutPred

0.62

.;Loss of methylation at K941 (P = 0.0946);

MVP

0.55

MPC

0.50

ClinPred

0.37

GERP RS

4.0

Varity_R

0.087

gMVP

0.23

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over