Variant 12-124947834-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_032656.4(DHX37):c.3442G>A(p.Glu1148Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000125 in 1,601,188 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00011 ( 1 hom. )

Consequence

DHX37
NM_032656.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.35

Variant links:

Genes affected

DHX37 (HGNC:17210): (DEAH-box helicase 37) This gene encodes a DEAD box protein. 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. [provided by RefSeq, Jul 2008]

DHX37 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0142630935).

BP6

Variant 12-124947834-C-T is Benign according to our data. Variant chr12-124947834-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2728144.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHX37	NM_032656.4 linkuse as main transcript	c.3442G>A	p.Glu1148Lys	missense_variant	27/27	ENST00000308736.7	NP_116045.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
DHX37	ENST00000308736.7 linkuse as main transcript	c.3442G>A	p.Glu1148Lys	missense_variant	27/27	1	NM_032656.4	ENSP00000311135	P1
DHX37	ENST00000544745.2 linkuse as main transcript	c.*110G>A		3_prime_UTR_variant	23/23	1		ENSP00000439009
DHX37	ENST00000507267.2 linkuse as main transcript	n.586G>A		non_coding_transcript_exon_variant	2/2	1
DHX37	ENST00000542400.5 linkuse as main transcript	n.2056G>A		non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes

AF:

0.000243

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

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:

0.00160

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000226

AC:

AN:

239036

Hom.:

AF XY:

0.000202

AC XY:

AN XY:

128792

show subpopulations

Gnomad AFR exome

AF:

0.0000622

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000548

Gnomad SAS exome

AF:

0.0000351

Gnomad FIN exome

AF:

0.00197

Gnomad NFE exome

AF:

0.0000745

Gnomad OTH exome

AF:

0.000348

GnomAD4 exome

AF:

0.000112

AC:

163

AN:

1449004

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

719444

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000237

Gnomad4 FIN exome

AF:

0.00212

Gnomad4 NFE exome

AF:

0.0000326

Gnomad4 OTH exome

AF:

0.000134

GnomAD4 genome

AF:

0.000243

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00160

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000116

Hom.:

Bravo

AF:

0.000102

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000140

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 24, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.78

DEOGEN2

Benign

0.014

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.46

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.79

M_CAP

Benign

0.0069

MetaRNN

Benign

0.014

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.4

MutationTaster

Benign

0.88

D;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.49

REVEL

Benign

0.035

Sift

Benign

0.79

Sift4G

Benign

0.67

Polyphen

0.42

Vest4

0.14

MVP

0.40

MPC

0.25

ClinPred

0.029

GERP RS

1.9

Varity_R

0.017

gMVP

0.30

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