Genetic Variant HTATSF1:p.Asp147Asp (chrX-136500689-T-C) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_014500.5(HTATSF1):c.441T>C(p.Asp147Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000155 in 1,146,759 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 47 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00071 ( 0 hom., 21 hem., cov: 24)

Exomes 𝑓: 0.000095 ( 0 hom. 26 hem. )

Consequence

HTATSF1
NM_014500.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.498

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 Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant X-136500689-T-C is Benign according to our data. Variant chrX-136500689-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2661520.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.498 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 21 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTATSF1	NM_014500.5 link	c.441T>C	p.Asp147Asp	synonymous_variant	Exon 4 of 9	ENST00000218364.5	NP_055315.2	O43719
HTATSF1	NM_001163280.2 link	c.441T>C	p.Asp147Asp	synonymous_variant	Exon 5 of 10		NP_001156752.1	O43719

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HTATSF1	ENST00000218364.5 link	c.441T>C	p.Asp147Asp	synonymous_variant	Exon 4 of 9	1	NM_014500.5	ENSP00000218364.4	O43719
HTATSF1	ENST00000535601.5 link	c.441T>C	p.Asp147Asp	synonymous_variant	Exon 5 of 10	1		ENSP00000442699.1	O43719
HTATSF1	ENST00000448450.5 link	c.441T>C	p.Asp147Asp	synonymous_variant	Exon 5 of 6	5		ENSP00000411381.1	Q5H918
HTATSF1	ENST00000425695.5 link	c.441T>C	p.Asp147Asp	synonymous_variant	Exon 5 of 6	3		ENSP00000412420.1	Q5H919

Frequencies

GnomAD3 genomes

AF:

0.000710

AC:

AN:

112662

Hom.:

Cov.:

AF XY:

0.000603

AC XY:

AN XY:

34816

show subpopulations

Gnomad AFR

AF:

0.00229

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000562

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00422

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00131

GnomAD3 exomes

AF:

0.000214

AC:

AN:

140455

Hom.:

AF XY:

0.000150

AC XY:

AN XY:

46611

show subpopulations

Gnomad AFR exome

AF:

0.00264

Gnomad AMR exome

AF:

0.000134

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000948

AC:

AN:

1034045

Hom.:

Cov.:

AF XY:

0.0000799

AC XY:

AN XY:

325229

show subpopulations

Gnomad4 AFR exome

AF:

0.00373

Gnomad4 AMR exome

AF:

0.000130

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:

0.00000123

Gnomad4 OTH exome

AF:

0.000138

GnomAD4 genome

AF:

0.000710

AC:

AN:

112714

Hom.:

Cov.:

AF XY:

0.000602

AC XY:

AN XY:

34878

show subpopulations

Gnomad4 AFR

AF:

0.00229

Gnomad4 AMR

AF:

0.000561

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:

0.00130

Alfa

AF:

0.000569

Hom.:

Bravo

AF:

0.000722

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

HTATSF1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

7.7

DANN

Benign

0.55

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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