rs73319052

Variant names:

• chr17-45169741-C-A
• rs73319052
• NM_001303441.2:c.793C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-45169741-C-A
• chr17-45169741-C-G
• chr17-45169741-C-T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BS1 BS2

The NM_001303441.2(HEXIM2):​c.793C>A​(p.Arg265Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000883 in 1,484,772 control chromosomes in the GnomAD database, including 16 homozygotes. 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: 𝑓 0.0047 (6 hom., cov: 31)
  • Exomes 𝑓: 0.00045 (10 hom.)
• Consequence: HEXIM2 NM_001303441.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0870
• Publications: 0 publications found

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-AS2 (HGNC:56693):

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP7: Synonymous conserved (PhyloP=-0.087 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00466 (710/152224) while in subpopulation AFR AF = 0.0168 (696/41548). AF 95% confidence interval is 0.0157. There are 6 homozygotes in GnomAd4. There are 332 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEXIM2	NM_001303441.2	MANE Select	c.793C>A	p.Arg265Arg	synonymous	Exon 4 of 4	NP_001290370.1	Q96MH2
	HEXIM2	NM_001303436.1		c.859C>A	p.Arg287Arg	synonymous	Exon 3 of 3	NP_001290365.1	Q96MH2
	HEXIM2	NM_001303437.1		c.793C>A	p.Arg265Arg	synonymous	Exon 4 of 4	NP_001290366.1	Q96MH2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEXIM2	ENST00000589230.6	TSL:2 MANE Select	c.793C>A	p.Arg265Arg	synonymous	Exon 4 of 4	ENSP00000466200.2	Q96MH2
	HEXIM2	ENST00000591576.5	TSL:1	c.793C>A	p.Arg265Arg	synonymous	Exon 3 of 3	ENSP00000465727.1	Q96MH2
	HEXIM2	ENST00000592695.1	TSL:1	c.793C>A	p.Arg265Arg	synonymous	Exon 3 of 3	ENSP00000467517.1	Q96MH2

Frequencies

GnomAD3 genomes AF: 0.00467 AC: 710 AN: 152106 Hom.: 6 Cov.: 31

Gnomad AFR AF: 0.0168

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

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: 0.0000147

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00137 AC: 140 AN: 101880 AF XY: 0.00110

Gnomad AFR exome AF: 0.0168

Gnomad AMR exome AF: 0.000861

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000246

Gnomad OTH exome AF: 0.000678

GnomAD4 exome AF: 0.000451 AC: 601 AN: 1332548 Hom.: 10 Cov.: 30 AF XY: 0.000418 AC XY: 272 AN XY: 651218

African (AFR) AF: 0.0182 AC: 531 AN: 29232

American (AMR) AF: 0.000946 AC: 24 AN: 25382

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21380

East Asian (EAS) AF: 0.00 AC: 0 AN: 35076

South Asian (SAS) AF: 0.0000140 AC: 1 AN: 71176

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41850

Middle Eastern (MID) AF: 0.000561 AC: 3 AN: 5348

European-Non Finnish (NFE) AF: 0.00000668 AC: 7 AN: 1048122

Other (OTH) AF: 0.000637 AC: 35 AN: 54982

GnomAD4 genome AF: 0.00466 AC: 710 AN: 152224 Hom.: 6 Cov.: 31 AF XY: 0.00446 AC XY: 332 AN XY: 74416

African (AFR) AF: 0.0168 AC: 696 AN: 41548

American (AMR) AF: 0.000654 AC: 10 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68002

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00107 Hom.: 0

Bravo AF: 0.00550

Asia WGS AF: 0.00144 AC: 6 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	12
DANN	Benign	0.80
PhyloP100		-0.087
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs73319052; hg19: chr17-43247108;