Genetic Variant HEXIM2:p.Arg265Arg (chr17-45169743-G-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_001303441.2(HEXIM2):c.795G>A(p.Arg265Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HEXIM2
NM_001303441.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.356

Publications

0 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:

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new If you want to explore the variant's impact on the transcript NM_001303441.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP7

Synonymous conserved (PhyloP=0.356 with no splicing effect.

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.795G>A	p.Arg265Arg	synonymous	Exon 4 of 4	NP_001290370.1	Q96MH2
HEXIM2	NM_001303436.1		c.861G>A	p.Arg287Arg	synonymous	Exon 3 of 3	NP_001290365.1	Q96MH2
HEXIM2	NM_001303437.1		c.795G>A	p.Arg265Arg	synonymous	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.795G>A	p.Arg265Arg	synonymous	Exon 4 of 4	ENSP00000466200.2	Q96MH2
HEXIM2	ENST00000591576.5	TSL:1	c.795G>A	p.Arg265Arg	synonymous	Exon 3 of 3	ENSP00000465727.1	Q96MH2
HEXIM2	ENST00000592695.1	TSL:1	c.795G>A	p.Arg265Arg	synonymous	Exon 3 of 3	ENSP00000467517.1	Q96MH2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

98904

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1330462

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

649952

African (AFR)

AF:

0.00

AC:

AN:

29208

American (AMR)

AF:

0.00

AC:

AN:

25218

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21196

East Asian (EAS)

AF:

0.00

AC:

AN:

35078

South Asian (SAS)

AF:

0.00

AC:

AN:

70604

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41344

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5354

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1047516

Other (OTH)

AF:

0.00

AC:

AN:

54944

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

0.36

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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