Genetic Variant HTATSF1:p.Ser40Phe (chrX-136497803-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014500.5(HTATSF1):c.119C>T(p.Ser40Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000417 in 1,198,770 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 9.2e-7 ( 0 hom. 1 hem. )

Consequence

HTATSF1
NM_014500.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.86

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:

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ACMG classification

Classification made for transcript

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=0.21583834).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTATSF1	NM_014500.5 link	c.119C>T	p.Ser40Phe	missense_variant	Exon 1 of 9	ENST00000218364.5	NP_055315.2	O43719
HTATSF1	NM_001163280.2 link	c.119C>T	p.Ser40Phe	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.119C>T	p.Ser40Phe	missense_variant	Exon 1 of 9	1	NM_014500.5	ENSP00000218364.4	O43719
HTATSF1	ENST00000535601.5 link	c.119C>T	p.Ser40Phe	missense_variant	Exon 2 of 10	1		ENSP00000442699.1	O43719
HTATSF1	ENST00000448450.5 link	c.119C>T	p.Ser40Phe	missense_variant	Exon 2 of 6	5		ENSP00000411381.1	Q5H918
HTATSF1	ENST00000425695.5 link	c.119C>T	p.Ser40Phe	missense_variant	Exon 2 of 6	3		ENSP00000412420.1	Q5H919

Frequencies

GnomAD3 genomes

AF:

0.0000356

AC:

AN:

112398

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34544

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000278

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000664

GnomAD4 exome

AF:

9.20e-7

AC:

AN:

1086372

Hom.:

Cov.:

AF XY:

0.00000282

AC XY:

AN XY:

354224

show subpopulations

Gnomad4 AFR exome

AF:

0.0000382

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

AF:

0.0000356

AC:

AN:

112398

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34544

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000278

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000664

Bravo

AF:

0.0000567

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.119C>T (p.S40F) alteration is located in exon 2 (coding exon 1) of the HTATSF1 gene. This alteration results from a C to T substitution at nucleotide position 119, causing the serine (S) at amino acid position 40 to be replaced by a phenylalanine (F). 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

0.12

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;T;T;T

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.78

T;T;T;.

M_CAP

Benign

0.020

MetaRNN

Benign

0.22

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

M;.;.;M

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.1

N;N;N;N

REVEL

Benign

0.095

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Uncertain

0.018

D;T;T;D

Polyphen

1.0

D;.;.;D

Vest4

0.27

MutPred

0.17

Loss of glycosylation at S40 (P = 0.0076);Loss of glycosylation at S40 (P = 0.0076);Loss of glycosylation at S40 (P = 0.0076);Loss of glycosylation at S40 (P = 0.0076);

MVP

0.44

MPC

1.3

ClinPred

0.95

GERP RS

4.5

Varity_R

0.29

gMVP

0.54

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