17-45150230-G-C

Variant names:

• chr17-45150230-G-C
• NM_006460.3:c.1040G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006460.3(HEXIM1):​c.1040G>C​(p.Arg347Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,376 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: HEXIM1 NM_006460.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.01

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]

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEXIM1	NM_006460.3	c.1040G>C	p.Arg347Pro	missense_variant	Exon 1 of 1	ENST00000332499.4	NP_006451.1
HEXIM2-AS1	NR_186788.1	n.768C>G		non_coding_transcript_exon_variant	Exon 2 of 2
HEXIM2-AS1	NR_186789.1	n.931C>G		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HEXIM1	ENST00000332499.4	c.1040G>C	p.Arg347Pro	missense_variant	Exon 1 of 1	6	NM_006460.3	ENSP00000328773.3
HEXIM2-AS1	ENST00000589950.1	n.*170C>G		downstream_gene_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457376 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 724202

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.52	D
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-0.34	T
MutationAssessor	Benign	1.5	L
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.42
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.054	T
Polyphen		0.99	D
Vest4		0.53
MutPred		0.20		Loss of helix (P = 0.0068);
MVP		0.50
MPC		2.4
ClinPred		0.96	D
GERP RS		4.4
Varity_R		0.78
gMVP		0.72

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-43227597;