Variant chr12-124949995-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP5

The NM_032656.4(DHX37):c.3281C>T(p.Thr1094Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,458,274 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

DHX37
NM_032656.4 missense

Scores

Clinical Significance

Likely pathogenic no assertion criteria provided P:2

Conservation

PhyloP100: 9.60

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PP5

Variant 12-124949995-G-A is Pathogenic according to our data. Variant chr12-124949995-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 691930.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHX37	NM_032656.4 linkuse as main transcript	c.3281C>T	p.Thr1094Met	missense_variant	25/27	ENST00000308736.7	NP_116045.2
DHX37	XM_005253590.4 linkuse as main transcript	c.3281C>T	p.Thr1094Met	missense_variant	25/26		XP_005253647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
DHX37	ENST00000308736.7 linkuse as main transcript	c.3281C>T	p.Thr1094Met	missense_variant	25/27	1	NM_032656.4	ENSP00000311135	P1
DHX37	ENST00000544745.2 linkuse as main transcript	c.2753C>T	p.Thr918Met	missense_variant	22/23	1		ENSP00000439009
DHX37	ENST00000542400.5 linkuse as main transcript	n.1895C>T		non_coding_transcript_exon_variant	4/6	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000819

AC:

AN:

244120

Hom.:

AF XY:

0.0000151

AC XY:

AN XY:

132520

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:

0.0000669

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1458274

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

725026

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:

0.0000584

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Intellectual disability;C4022738:Neurodevelopmental delay

Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

May 30, 2019

- -

Neurodevelopmental disorders

Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

University of Washington Center for Mendelian Genomics, University of Washington

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Uncertain

0.057

BayesDel_noAF

Uncertain

0.030

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.27

T;T

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.83

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

D;.

M_CAP

Benign

0.033

MetaRNN

Uncertain

0.74

D;D

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.4

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-4.2

D;D

REVEL

Uncertain

0.51

Sift

Uncertain

0.0060

D;D

Sift4G

Uncertain

0.015

D;T

Polyphen

1.0

D;D

Vest4

0.80

MutPred

0.49

Loss of methylation at K1093 (P = 0.0365);.;

MVP

0.63

MPC

0.78

ClinPred

0.77

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.27

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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