X-136499619-A-G

Variant names:

• chrX-136499619-A-G
• NM_014500.5:c.208A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014500.5(HTATSF1):​c.208A>G​(p.Thr70Ala) 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. 12/20 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: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: HTATSF1 NM_014500.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.32

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20364454).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTATSF1	NM_014500.5	c.208A>G	p.Thr70Ala	missense_variant	Exon 2 of 9	ENST00000218364.5	NP_055315.2
HTATSF1	NM_001163280.2	c.208A>G	p.Thr70Ala	missense_variant	Exon 3 of 10		NP_001156752.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTATSF1	ENST00000218364.5	c.208A>G	p.Thr70Ala	missense_variant	Exon 2 of 9	1	NM_014500.5	ENSP00000218364.4
HTATSF1	ENST00000535601.5	c.208A>G	p.Thr70Ala	missense_variant	Exon 3 of 10	1		ENSP00000442699.1
HTATSF1	ENST00000448450.5	c.208A>G	p.Thr70Ala	missense_variant	Exon 3 of 6	5		ENSP00000411381.1
HTATSF1	ENST00000425695.5	c.208A>G	p.Thr70Ala	missense_variant	Exon 3 of 6	3		ENSP00000412420.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1068420 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 345134

Gnomad4 AFR exome AF: 0.00

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.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 08, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.208A>G (p.T70A) alteration is located in exon 3 (coding exon 2) of the HTATSF1 gene. This alteration results from a A to G substitution at nucleotide position 208, causing the threonine (T) at amino acid position 70 to be replaced by an alanine (A). 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	Benign	0.099
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	18
DANN	Benign	0.50
DEOGEN2	Benign	0.048	T;T;T;T
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.78	T;T;T;.
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.20	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;.;.;L
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.67	N;N;N;N
REVEL	Benign	0.031
Sift	Benign	0.17	T;T;T;T
Sift4G	Benign	0.65	T;T;T;T
Polyphen		0.057	B;.;.;B
Vest4		0.21
MutPred		0.36		Loss of sheet (P = 0.0025);Loss of sheet (P = 0.0025);Loss of sheet (P = 0.0025);Loss of sheet (P = 0.0025);
MVP		0.56
MPC		0.49
ClinPred		0.63	D
GERP RS		4.4
Varity_R		0.12
gMVP		0.33

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: chrX-135581778;