Genetic Variant HTATSF1:p.Gln31Glu (chrX-136497775-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 9.2e-7 ( 0 hom. 0 hem. )

Consequence

HTATSF1
NM_014500.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00900

Variant links:

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]

HTATSF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.049953997).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTATSF1	NM_014500.5 link	c.91C>G	p.Gln31Glu	missense_variant	Exon 1 of 9	ENST00000218364.5	NP_055315.2	O43719
HTATSF1	NM_001163280.2 link	c.91C>G	p.Gln31Glu	missense_variant	Exon 2 of 10		NP_001156752.1	O43719

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HTATSF1	ENST00000218364.5 link	c.91C>G	p.Gln31Glu	missense_variant	Exon 1 of 9	1	NM_014500.5	ENSP00000218364.4	O43719
HTATSF1	ENST00000535601.5 link	c.91C>G	p.Gln31Glu	missense_variant	Exon 2 of 10	1		ENSP00000442699.1	O43719
HTATSF1	ENST00000448450.5 link	c.91C>G	p.Gln31Glu	missense_variant	Exon 2 of 6	5		ENSP00000411381.1	Q5H918
HTATSF1	ENST00000425695.5 link	c.91C>G	p.Gln31Glu	missense_variant	Exon 2 of 6	3		ENSP00000412420.1	Q5H919

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000556

AC:

AN:

179908

Hom.:

AF XY:

0.00

AC XY:

AN XY:

64636

show subpopulations

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 SAS 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:

AN:

1090333

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

357049

show subpopulations

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:

0.00000120

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.91C>G (p.Q31E) alteration is located in exon 2 (coding exon 1) of the HTATSF1 gene. This alteration results from a C to G substitution at nucleotide position 91, causing the glutamine (Q) at amino acid position 31 to be replaced by a glutamic acid (E). 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

0.057

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.91

CADD

Benign

7.0

DANN

Benign

0.68

DEOGEN2

Benign

0.057

T;T;T;T

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.63

T;T;T;.

M_CAP

Benign

0.0024

MetaRNN

Benign

0.050

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;.;.;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.57

N;N;N;N

REVEL

Benign

0.025

Sift

Benign

0.43

T;T;T;T

Sift4G

Benign

0.49

T;T;T;T

Polyphen

0.0

B;.;.;B

Vest4

0.060

MutPred

0.074

Loss of glycosylation at T32 (P = 0.2032);Loss of glycosylation at T32 (P = 0.2032);Loss of glycosylation at T32 (P = 0.2032);Loss of glycosylation at T32 (P = 0.2032);

MVP

0.26

MPC

0.54

ClinPred

0.020

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.076

gMVP

0.48

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over