HEXIM2 p.Thr241Ser

Variant names:

• chr17-45169669-A-T
• NM_001303441.2:c.721A>T
• HEXIM2 p.Thr241Ser

Your query was ambiguous. Multiple possible variants found:

• chr17-45169669-A-T
• chr17-45169670-C-G
• chr17-45169669-ACC-TCT
• chr17-45169669-ACC-TCA
• chr17-45169669-ACC-TCG
• chr17-45169670-CC-GT

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001303441.2(HEXIM2):​c.721A>T​(p.Thr241Ser) variant causes a missense 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. 16/21 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. T241I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: HEXIM2 NM_001303441.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.18
• 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: 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=0.040225297).

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.721A>T	p.Thr241Ser	missense	Exon 4 of 4	NP_001290370.1	Q96MH2
	HEXIM2	NM_001303436.1		c.787A>T	p.Thr263Ser	missense	Exon 3 of 3	NP_001290365.1	Q96MH2
	HEXIM2	NM_001303437.1		c.721A>T	p.Thr241Ser	missense	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.721A>T	p.Thr241Ser	missense	Exon 4 of 4	ENSP00000466200.2	Q96MH2
	HEXIM2	ENST00000591576.5	TSL:1	c.721A>T	p.Thr241Ser	missense	Exon 3 of 3	ENSP00000465727.1	Q96MH2
	HEXIM2	ENST00000592695.1	TSL:1	c.721A>T	p.Thr241Ser	missense	Exon 3 of 3	ENSP00000467517.1	Q96MH2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.39
DANN	Benign	0.65
DEOGEN2	Benign	0.018	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	M
PhyloP100		-2.2
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.0030
Sift	Benign	0.54	T
Sift4G	Benign	0.77	T
Varity_R		0.031
gMVP		0.046

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.

Other links and lift over

hg19: chr17-43247036;