NM_014500.5:c.91C>G

Variant names:

• chrX-136497775-C-G
• rs1156538917
• NM_014500.5:c.91C>G

Variant summary

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

The NM_014500.5(HTATSF1):​c.91C>G​(p.Gln31Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000917 in 1,090,333 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 9.2e-7 (0 hom. 0 hem.)
• Consequence: HTATSF1 NM_014500.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.00900
• Publications: 0 publications found

Genes affected

HTATSF1 (HGNC:5276): (HIV-1 Tat specific factor 1) The protein encoded by this gene functions as a cofactor for the stimulation of transcriptional elongation by HIV-1 Tat, which binds to the HIV-1 promoter through Tat-TAR interaction. This protein may also serve as a dual-function factor to couple transcription and splicing and to facilitate their reciprocal activation. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Sep 2009]

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=0.049953997).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014500.5. 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
	HTATSF1	NM_014500.5	MANE Select	c.91C>G	p.Gln31Glu	missense	Exon 1 of 9	NP_055315.2
	HTATSF1	NM_001163280.2		c.91C>G	p.Gln31Glu	missense	Exon 2 of 10	NP_001156752.1	O43719

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTATSF1	ENST00000218364.5	TSL:1 MANE Select	c.91C>G	p.Gln31Glu	missense	Exon 1 of 9	ENSP00000218364.4	O43719
	HTATSF1	ENST00000535601.5	TSL:1	c.91C>G	p.Gln31Glu	missense	Exon 2 of 10	ENSP00000442699.1	O43719
	HTATSF1	ENST00000866998.1		c.91C>G	p.Gln31Glu	missense	Exon 1 of 9	ENSP00000537057.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD2 exomes AF: 0.00000556 AC: 1 AN: 179908 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: 0.0000124

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 9.17e-7 AC: 1 AN: 1090333 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 357049

African (AFR) AF: 0.00 AC: 0 AN: 26259

American (AMR) AF: 0.00 AC: 0 AN: 35011

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19222

East Asian (EAS) AF: 0.00 AC: 0 AN: 29914

South Asian (SAS) AF: 0.00 AC: 0 AN: 53446

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40313

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4098

European-Non Finnish (NFE) AF: 0.00000120 AC: 1 AN: 836450

Other (OTH) AF: 0.00 AC: 0 AN: 45620

GnomAD4 genome Cov.: 24

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	0.057
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.0
DANN	Benign	0.68
DEOGEN2	Benign	0.057	T
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.0090
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.025
Sift	Benign	0.43	T
Sift4G	Benign	0.49	T
Polyphen		0.0	B
Vest4		0.060
MutPred		0.074		Loss of glycosylation at T32 (P = 0.2032)
MVP		0.26
MPC		0.54
ClinPred		0.020	T
GERP RS		1.9
PromoterAI		0.039	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.076
gMVP		0.48
Mutation Taster		=94/6	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: rs1156538917; hg19: chrX-135579934;