Genetic Variant HEXIM1:p.Gly65Glu (chr17-45149384-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006460.3(HEXIM1):c.194G>A(p.Gly65Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

HEXIM1
NM_006460.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.20

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13789418).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEXIM1	NM_006460.3	MANE Select	c.194G>A	p.Gly65Glu	missense	Exon 1 of 1	NP_006451.1	O94992

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HEXIM1	ENST00000332499.4	TSL:6 MANE Select	c.194G>A	p.Gly65Glu	missense	Exon 1 of 1	ENSP00000328773.3	O94992
HEXIM2-AS1	ENST00000589950.2	TSL:4	n.1614C>T		non_coding_transcript_exon	Exon 2 of 2
HEXIM2-AS1	ENST00000837780.1		n.777C>T		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41448

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

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

0.097

BayesDel_addAF

Benign

0.0039

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.65

M_CAP

Benign

0.024

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.68

MutationAssessor

Benign

0.90

PhyloP100

2.2

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.090

REVEL

Benign

0.22

Sift

Uncertain

0.0070

Sift4G

Benign

0.11

Polyphen

0.98

Vest4

0.089

MutPred

0.11

Loss of glycosylation at S66 (P = 0.0759)

MVP

0.18

MPC

1.3

ClinPred

0.78

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.17

gMVP

0.072

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over