X-136510832-G-C

Variant names:

• chrX-136510832-G-C
• rs755368281
• NM_014500.5:c.1087G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014500.5(HTATSF1):​c.1087G>C​(p.Glu363Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: HTATSF1 NM_014500.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.30

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37728947).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTATSF1	NM_014500.5	c.1087G>C	p.Glu363Gln	missense_variant	Exon 9 of 9	ENST00000218364.5	NP_055315.2
HTATSF1	NM_001163280.2	c.1087G>C	p.Glu363Gln	missense_variant	Exon 10 of 10		NP_001156752.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTATSF1	ENST00000218364.5	c.1087G>C	p.Glu363Gln	missense_variant	Exon 9 of 9	1	NM_014500.5	ENSP00000218364.4
HTATSF1	ENST00000535601.5	c.1087G>C	p.Glu363Gln	missense_variant	Exon 10 of 10	1		ENSP00000442699.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

Bravo AF: 0.0000151

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 22, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1087G>C (p.E363Q) alteration is located in exon 10 (coding exon 9) of the HTATSF1 gene. This alteration results from a G to C substitution at nucleotide position 1087, causing the glutamic acid (E) at amino acid position 363 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.088	T;T
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.93	D;.
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.38	T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.6	M;M
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Benign	0.085
Sift	Uncertain	0.024	D;D
Sift4G	Uncertain	0.016	D;D
Polyphen		1.0	D;D
Vest4		0.37
MutPred		0.18		Gain of MoRF binding (P = 0.0354);Gain of MoRF binding (P = 0.0354);
MVP		0.79
MPC		0.85
ClinPred		0.96	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.46
gMVP		0.89

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

LitVar

Other links and lift over

dbSNP: rs755368281; hg19: chrX-135592991;