Genetic Variant HEXIM2:p.Arg279His (chr17-45169784-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001303441.2(HEXIM2):c.836G>A(p.Arg279His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000136 in 1,448,468 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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. R279L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000093 ( 2 hom. )

Consequence

HEXIM2
NM_001303441.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.700

Publications

1 publications found

Variant links:

Genes affected

HEXIM2 (HGNC:28591): (HEXIM P-TEFb complex subunit 2) This gene encodes a member of the HEXIM family of proteins. This protein is a component of the 7SK small nuclear ribonucleoprotein. This protein has been found to negatively regulate the kinase activity of the cyclin-dependent kinase P-TEFb, which phosphorylates multiple target proteins to promote transcriptional elongation. This gene is located approximately 7 kb downstream from related family member HEXIM1 on chromosome 17. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

HEXIM2 links:

HEXIM2-AS2 (HGNC:56693):

HEXIM2-AS2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034602582).

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001303441.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HEXIM2	NM_001303441.2	MANE Select	c.836G>A	p.Arg279His	missense	Exon 4 of 4	NP_001290370.1	Q96MH2
HEXIM2	NM_001303436.1		c.902G>A	p.Arg301His	missense	Exon 3 of 3	NP_001290365.1	Q96MH2
HEXIM2	NM_001303437.1		c.836G>A	p.Arg279His	missense	Exon 4 of 4	NP_001290366.1	Q96MH2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HEXIM2	ENST00000589230.6	TSL:2 MANE Select	c.836G>A	p.Arg279His	missense	Exon 4 of 4	ENSP00000466200.2	Q96MH2
HEXIM2	ENST00000591576.5	TSL:1	c.836G>A	p.Arg279His	missense	Exon 3 of 3	ENSP00000465727.1	Q96MH2
HEXIM2	ENST00000592695.1	TSL:1	c.836G>A	p.Arg279His	missense	Exon 3 of 3	ENSP00000467517.1	Q96MH2

Frequencies

GnomAD3 genomes

AF:

0.000513

AC:

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00174

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000255

AC:

AN:

74524

AF XY:

0.000188

show subpopulations

Gnomad AFR exome

AF:

0.00237

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000317

Gnomad OTH exome

AF:

0.000428

GnomAD4 exome

AF:

0.0000926

AC:

120

AN:

1296250

Hom.:

Cov.:

AF XY:

0.0000890

AC XY:

AN XY:

629248

show subpopulations

African (AFR)

AF:

0.00294

AC:

AN:

28528

American (AMR)

AF:

0.000186

AC:

AN:

21464

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19346

East Asian (EAS)

AF:

0.00

AC:

AN:

34826

South Asian (SAS)

AF:

0.0000309

AC:

AN:

64780

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34450

Middle Eastern (MID)

AF:

0.000790

AC:

AN:

5064

European-Non Finnish (NFE)

AF:

0.0000193

AC:

AN:

1033996

Other (OTH)

AF:

0.000112

AC:

AN:

53796

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000506

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.00171

AC:

AN:

41532

American (AMR)

AF:

0.000196

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000207

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68002

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000267

Hom.:

Bravo

AF:

0.000661

ESP6500AA

AF:

0.00217

AC:

ESP6500EA

AF:

0.000125

AC:

ExAC

AF:

0.000166

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.64

(source)

DANN

Benign

0.63

DEOGEN2

Benign

0.011

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.41

M_CAP

Benign

0.0054

MetaRNN

Benign

0.0035

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

-0.70

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.36

REVEL

Benign

0.0010

Sift

Benign

0.54

Sift4G

Benign

0.38

Polyphen

0.0010

Vest4

0.10

MVP

0.22

MPC

0.63

ClinPred

0.0022

GERP RS

-1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.013

gMVP

0.040

Mutation Taster

=91/9

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over