Genetic Variant HEXIM1:p.His123Arg (chr17-45149558-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006460.3(HEXIM1):c.368A>G(p.His123Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H123P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

HEXIM1
NM_006460.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.715

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.024285674).

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.368A>G	p.His123Arg	missense	Exon 1 of 1	NP_006451.1	O94992
HEXIM2-AS1	NR_186788.1		n.*104T>C		downstream_gene	N/A
HEXIM2-AS1	NR_186789.1		n.*104T>C		downstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HEXIM1	ENST00000332499.4	TSL:6 MANE Select	c.368A>G	p.His123Arg	missense	Exon 1 of 1	ENSP00000328773.3	O94992
HEXIM2-AS1	ENST00000589950.2	TSL:4	n.1440T>C		non_coding_transcript_exon	Exon 2 of 2
HEXIM2-AS1	ENST00000837780.1		n.603T>C		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455702

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723882

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33382

American (AMR)

AF:

0.00

AC:

AN:

43308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26028

East Asian (EAS)

AF:

0.00

AC:

AN:

39468

South Asian (SAS)

AF:

0.00

AC:

AN:

85874

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52136

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

9.01e-7

AC:

AN:

1109584

Other (OTH)

AF:

0.00

AC:

AN:

60160

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.73

CADD

Benign

5.3

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.12

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.28

M_CAP

Benign

0.0060

MetaRNN

Benign

0.024

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PhyloP100

0.71

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.55

REVEL

Benign

0.029

Sift

Benign

0.78

Sift4G

Benign

0.73

Polyphen

0.0

Vest4

0.060

MutPred

0.11

Gain of solvent accessibility (P = 0.039)

MVP

0.082

MPC

1.1

ClinPred

0.032

GERP RS

-1.1

Varity_R

0.037

gMVP

0.033

Mutation Taster

=97/3

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over