16-72096204-C-G

Position:

chr16-72096204-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_014003.4(DHX38):c.47C>G(p.Thr16Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0223 in 1,612,508 control chromosomes in the GnomAD database, including 514 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 26 hom., cov: 32)

Exomes 𝑓: 0.023 ( 488 hom. )

Consequence

DHX38
NM_014003.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.76

Variant links:

Genes affected

DHX38 (HGNC:17211): (DEAH-box helicase 38) 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. The protein encoded by this gene is a member of the DEAD/H box family of splicing factors. This protein resembles yeast Prp16 more closely than other DEAD/H family members. It is an ATPase and essential for the catalytic step II in pre-mRNA splicing process. [provided by RefSeq, Jul 2008]

DHX38 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0048604608).

BP6

Variant 16-72096204-C-G is Benign according to our data. Variant chr16-72096204-C-G is described in ClinVar as [Benign]. Clinvar id is 1170732.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-72096204-C-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0156 (2374/152292) while in subpopulation NFE AF= 0.0227 (1543/68024). AF 95% confidence interval is 0.0217. There are 26 homozygotes in gnomad4. There are 1150 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHX38	NM_014003.4 linkuse as main transcript	c.47C>G	p.Thr16Ser	missense_variant	2/27	ENST00000268482.8	NP_054722.2	Q92620-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DHX38	ENST00000268482.8 linkuse as main transcript	c.47C>G	p.Thr16Ser	missense_variant	2/27	1	NM_014003.4	ENSP00000268482.3	Q92620-1
DHX38	ENST00000566794.5 linkuse as main transcript	c.47C>G	p.Thr16Ser	missense_variant	2/3	4		ENSP00000455939.1	H3BQT9
DHX38	ENST00000566489.1 linkuse as main transcript	c.47C>G	p.Thr16Ser	missense_variant	3/4	4		ENSP00000457887.1	H3BV01
DHX38	ENST00000579387.5 linkuse as main transcript	n.47C>G		non_coding_transcript_exon_variant	2/12	5		ENSP00000462149.1	J3KRT1

Frequencies

GnomAD3 genomes

AF:

0.0156

AC:

2373

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00427

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.00837

Gnomad ASJ

AF:

0.0107

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0222

Gnomad FIN

AF:

0.0299

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0227

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.0186

AC:

4648

AN:

250552

Hom.:

AF XY:

0.0198

AC XY:

2689

AN XY:

135566

show subpopulations

Gnomad AFR exome

AF:

0.00451

Gnomad AMR exome

AF:

0.00567

Gnomad ASJ exome

AF:

0.0121

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0263

Gnomad FIN exome

AF:

0.0311

Gnomad NFE exome

AF:

0.0234

Gnomad OTH exome

AF:

0.0224

GnomAD4 exome

AF:

0.0230

AC:

33563

AN:

1460216

Hom.:

488

Cov.:

AF XY:

0.0231

AC XY:

16790

AN XY:

726062

show subpopulations

Gnomad4 AFR exome

AF:

0.00392

Gnomad4 AMR exome

AF:

0.00577

Gnomad4 ASJ exome

AF:

0.0104

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.0276

Gnomad4 FIN exome

AF:

0.0334

Gnomad4 NFE exome

AF:

0.0246

Gnomad4 OTH exome

AF:

0.0210

GnomAD4 genome

AF:

0.0156

AC:

2374

AN:

152292

Hom.:

Cov.:

AF XY:

0.0154

AC XY:

1150

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00426

Gnomad4 AMR

AF:

0.00836

Gnomad4 ASJ

AF:

0.0107

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0222

Gnomad4 FIN

AF:

0.0299

Gnomad4 NFE

AF:

0.0227

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.0193

Hom.:

Bravo

AF:

0.0131

TwinsUK

AF:

0.0240

AC:

ALSPAC

AF:

0.0241

AC:

ESP6500AA

AF:

0.00432

AC:

ESP6500EA

AF:

0.0221

AC:

190

ExAC

AF:

0.0192

AC:

2327

Asia WGS

AF:

0.00895

AC:

AN:

3478

EpiCase

AF:

0.0210

EpiControl

AF:

0.0213

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.039

T;.;.

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.69

T;T;T

MetaRNN

Benign

0.0049

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.97

L;.;.

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.21

N;N;N

REVEL

Benign

0.048

Sift

Benign

0.56

T;T;T

Sift4G

Benign

0.64

T;T;T

Polyphen

0.0010

B;.;.

Vest4

0.029

MutPred

0.23

Gain of disorder (P = 0.0239);Gain of disorder (P = 0.0239);Gain of disorder (P = 0.0239);

MPC

0.18

ClinPred

0.0017

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.034

gMVP

0.15

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