Genetic Variant NM_006460.3:c.239C>A (chr17-45149429-C-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_006460.3(HEXIM1):c.239C>A(p.Pro80Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000441 in 1,613,224 control chromosomes in the GnomAD database, including 1 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 (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00046 ( 1 hom. )

Consequence

HEXIM1
NM_006460.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.36

Publications

3 publications found

Variant links:

Genes affected

HEXIM1 (HGNC:24953): (HEXIM P-TEFb complex subunit 1) Expression of this gene is induced by hexamethylene-bis-acetamide in vascular smooth muscle cells. This gene has no introns. [provided by RefSeq, Jul 2008]

HEXIM1 links:

HEXIM2-AS1 (HGNC:55857): (HEXIM2 antisense RNA 1)

HEXIM2-AS1 links:

ENSG00000276728 (HGNC:):

ENSG00000276728 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=0.027988166).

BS2

High AC in GnomAd4 at 42 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006460.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HEXIM1	NM_006460.3	MANE Select	c.239C>A	p.Pro80Gln	missense	Exon 1 of 1	NP_006451.1	O94992
HEXIM2-AS1	NR_186788.1		n.*233G>T		downstream_gene	N/A
HEXIM2-AS1	NR_186789.1		n.*233G>T		downstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HEXIM1	ENST00000332499.4	TSL:6 MANE Select	c.239C>A	p.Pro80Gln	missense	Exon 1 of 1	ENSP00000328773.3	O94992
HEXIM2-AS1	ENST00000589950.2	TSL:4	n.1569G>T		non_coding_transcript_exon	Exon 2 of 2
HEXIM2-AS1	ENST00000837780.1		n.732G>T		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000529

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000286

AC:

AN:

248380

AF XY:

0.000326

show subpopulations

Gnomad AFR exome

AF:

0.000192

Gnomad AMR exome

AF:

0.000405

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000466

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000459

AC:

670

AN:

1460918

Hom.:

Cov.:

AF XY:

0.000453

AC XY:

329

AN XY:

726710

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33480

American (AMR)

AF:

0.000313

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.0000570

AC:

AN:

52614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000550

AC:

611

AN:

1111884

Other (OTH)

AF:

0.000663

AC:

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

128

170

213

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<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:

0.000276

AC:

AN:

152306

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.0000240

AC:

AN:

41594

American (AMR)

AF:

0.000131

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5144

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000529

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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:

0.000447

Hom.:

Bravo

AF:

0.000336

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000280

AC:

EpiCase

AF:

0.000763

EpiControl

AF:

0.000534

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

0.077

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.16

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.47

M_CAP

Benign

0.015

MetaRNN

Benign

0.028

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.6

PhyloP100

1.4

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.27

REVEL

Benign

0.038

Sift

Benign

0.13

Sift4G

Benign

0.62

Polyphen

0.34

Vest4

0.11

MVP

0.14

MPC

1.2

ClinPred

0.029

GERP RS

1.9

Varity_R

0.045

gMVP

0.077

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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