Genetic Variant HTATSF1:p.Val491Ile (chrX-136511216-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_014500.5(HTATSF1):c.1471G>A(p.Val491Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000117 in 1,206,682 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 44 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., 8 hem., cov: 22)

Exomes 𝑓: 0.00011 ( 0 hom. 36 hem. )

Consequence

HTATSF1
NM_014500.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.564

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.026779443).

BS2

High Hemizygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTATSF1	NM_014500.5 link	c.1471G>A	p.Val491Ile	missense_variant	Exon 9 of 9	ENST00000218364.5	NP_055315.2	O43719
HTATSF1	NM_001163280.2 link	c.1471G>A	p.Val491Ile	missense_variant	Exon 10 of 10		NP_001156752.1	O43719

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTATSF1	ENST00000218364.5 link	c.1471G>A	p.Val491Ile	missense_variant	Exon 9 of 9	1	NM_014500.5	ENSP00000218364.4		O43719
HTATSF1	ENST00000535601.5 link	c.1471G>A	p.Val491Ile	missense_variant	Exon 10 of 10	1		ENSP00000442699.1		O43719

Frequencies

GnomAD3 genomes

AF:

0.000179

AC:

AN:

111470

Hom.:

Cov.:

AF XY:

0.000238

AC XY:

AN XY:

33670

show subpopulations

Gnomad AFR

AF:

0.000359

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000151

Gnomad OTH

AF:

0.000672

GnomAD3 exomes

AF:

0.0000618

AC:

AN:

177931

Hom.:

AF XY:

0.0000470

AC XY:

AN XY:

63851

show subpopulations

Gnomad AFR exome

AF:

0.000235

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000113

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000749

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000110

AC:

121

AN:

1095212

Hom.:

Cov.:

AF XY:

0.0000997

AC XY:

AN XY:

361216

show subpopulations

Gnomad4 AFR exome

AF:

0.000574

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000562

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000114

Gnomad4 OTH exome

AF:

0.000152

GnomAD4 genome

AF:

0.000179

AC:

AN:

111470

Hom.:

Cov.:

AF XY:

0.000238

AC XY:

AN XY:

33670

show subpopulations

Gnomad4 AFR

AF:

0.000359

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000151

Gnomad4 OTH

AF:

0.000672

Alfa

AF:

0.000427

Hom.:

Bravo

AF:

0.000234

ExAC

AF:

0.0000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 25, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1471G>A (p.V491I) alteration is located in exon 10 (coding exon 9) of the HTATSF1 gene. This alteration results from a G to A substitution at nucleotide position 1471, causing the valine (V) at amino acid position 491 to be replaced by an isoleucine (I). 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

0.065

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.057

DANN

Benign

0.58

DEOGEN2

Benign

0.046

T;T

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.098

T;.

M_CAP

Benign

0.0018

MetaRNN

Benign

0.027

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.69

N;N

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.24

N;N

REVEL

Benign

0.0060

Sift

Benign

0.18

T;T

Sift4G

Benign

0.18

T;T

Polyphen

0.0

B;B

Vest4

0.065

MVP

0.13

MPC

0.40

ClinPred

0.012

GERP RS

-4.4

Varity_R

0.041

gMVP

0.012

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