rs1479401477

Variant names:

• chr17-45149488-G-A
• rs1479401477
• NM_006460.3:c.298G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-45149488-G-A
• chr17-45149488-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006460.3(HEXIM1):​c.298G>A​(p.Gly100Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,370 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: HEXIM1 NM_006460.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.61
• Publications: 0 publications found

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)

ENSG00000276728 (HGNC:):

ACMG classification

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=0.11307976).

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.298G>A	p.Gly100Ser	missense	Exon 1 of 1	NP_006451.1	O94992
	HEXIM2-AS1	NR_186788.1		n.*174C>T		downstream_gene	N/A
	HEXIM2-AS1	NR_186789.1		n.*174C>T		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEXIM1	ENST00000332499.4	TSL:6 MANE Select	c.298G>A	p.Gly100Ser	missense	Exon 1 of 1	ENSP00000328773.3	O94992
	HEXIM2-AS1	ENST00000589950.2	TSL:4	n.1510C>T		non_coding_transcript_exon	Exon 2 of 2
	HEXIM2-AS1	ENST00000837780.1		n.673C>T		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000422 AC: 1 AN: 236768 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: 0.0000565

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458370 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 725378

African (AFR) AF: 0.00 AC: 0 AN: 33432

American (AMR) AF: 0.00 AC: 0 AN: 44210

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26082

East Asian (EAS) AF: 0.0000505 AC: 2 AN: 39600

South Asian (SAS) AF: 0.00 AC: 0 AN: 86126

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51926

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111002

Other (OTH) AF: 0.00 AC: 0 AN: 60226

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.083	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.6
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.044
Sift	Benign	0.076	T
Sift4G	Benign	0.29	T
Polyphen		0.0030	B
Vest4		0.20
MutPred		0.12		Gain of glycosylation at G100 (P = 0.0034)
MVP		0.14
MPC		1.4
ClinPred		0.095	T
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.095
gMVP		0.073
Mutation Taster		=97/3	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: rs1479401477; hg19: chr17-43226855;