X-136497856-G-T

Variant names:

• chrX-136497856-G-T
• NM_014500.5:c.172G>T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_014500.5(HTATSF1):​c.172G>T​(p.Ala58Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000378 in 1,057,087 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000038 (0 hom. 3 hem.)
• Consequence: HTATSF1 NM_014500.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.09

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTATSF1	NM_014500.5	c.172G>T	p.Ala58Ser	missense_variant	Exon 1 of 9	ENST00000218364.5	NP_055315.2
HTATSF1	NM_001163280.2	c.172G>T	p.Ala58Ser	missense_variant	Exon 2 of 10		NP_001156752.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTATSF1	ENST00000218364.5	c.172G>T	p.Ala58Ser	missense_variant	Exon 1 of 9	1	NM_014500.5	ENSP00000218364.4
HTATSF1	ENST00000535601.5	c.172G>T	p.Ala58Ser	missense_variant	Exon 2 of 10	1		ENSP00000442699.1
HTATSF1	ENST00000448450.5	c.172G>T	p.Ala58Ser	missense_variant	Exon 2 of 6	5		ENSP00000411381.1
HTATSF1	ENST00000425695.5	c.172G>T	p.Ala58Ser	missense_variant	Exon 2 of 6	3		ENSP00000412420.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000378 AC: 4 AN: 1057087 Hom.: 0 Cov.: 29 AF XY: 0.00000896 AC XY: 3 AN XY: 334761

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: 0.0000201

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000368

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

Feb 23, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.172G>T (p.A58S) alteration is located in exon 2 (coding exon 1) of the HTATSF1 gene. This alteration results from a G to T substitution at nucleotide position 172, causing the alanine (A) at amino acid position 58 to be replaced by a serine (S). 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	Pathogenic	0.74
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T;T;T;T
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	D;D;D;.
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.50	D;D;D;D
MetaSVM	Benign	-0.68	T
MutationAssessor	Pathogenic	3.3	M;.;.;M
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-2.7	D;D;D;D
REVEL	Benign	0.28
Sift	Uncertain	0.013	D;D;D;D
Sift4G	Uncertain	0.012	D;D;D;D
Polyphen		1.0	D;.;.;D
Vest4		0.54
MutPred		0.39		Loss of catalytic residue at A58 (P = 0.0028);Loss of catalytic residue at A58 (P = 0.0028);Loss of catalytic residue at A58 (P = 0.0028);Loss of catalytic residue at A58 (P = 0.0028);
MVP		0.85
MPC		1.3
ClinPred		0.99	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.72
gMVP		0.71

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-135580015;