Genetic Variant NM_014500.5:c.1471G>A (chrX-136511216-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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

Publications

1 publications found

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 was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

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

BS2

High Hemizygotes in GnomAd4 at 8 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014500.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTATSF1	NM_014500.5	MANE Select	c.1471G>A	p.Val491Ile	missense	Exon 9 of 9	NP_055315.2
	HTATSF1	NM_001163280.2		c.1471G>A	p.Val491Ile	missense	Exon 10 of 10	NP_001156752.1	O43719

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HTATSF1	ENST00000218364.5	TSL:1 MANE Select	c.1471G>A	p.Val491Ile	missense	Exon 9 of 9	ENSP00000218364.4	O43719
HTATSF1	ENST00000535601.5	TSL:1	c.1471G>A	p.Val491Ile	missense	Exon 10 of 10	ENSP00000442699.1	O43719
HTATSF1	ENST00000866998.1		c.1498G>A	p.Val500Ile	missense	Exon 9 of 9	ENSP00000537057.1

Frequencies

GnomAD3 genomes

AF:

0.000179

AC:

AN:

111470

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.0000618

AC:

AN:

177931

AF XY:

0.0000470

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 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

African (AFR)

AF:

0.000574

AC:

AN:

26112

American (AMR)

AF:

0.00

AC:

AN:

34533

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19230

East Asian (EAS)

AF:

0.00

AC:

AN:

30193

South Asian (SAS)

AF:

0.0000562

AC:

AN:

53400

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40489

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4112

European-Non Finnish (NFE)

AF:

0.000114

AC:

AN:

841204

Other (OTH)

AF:

0.000152

AC:

AN:

45939

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000179

AC:

AN:

111470

Hom.:

Cov.:

AF XY:

0.000238

AC XY:

AN XY:

33670

show subpopulations

African (AFR)

AF:

0.000359

AC:

AN:

30660

American (AMR)

AF:

0.00

AC:

AN:

10480

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2638

East Asian (EAS)

AF:

0.00

AC:

AN:

3568

South Asian (SAS)

AF:

0.00

AC:

AN:

2658

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5964

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.000151

AC:

AN:

53089

Other (OTH)

AF:

0.000672

AC:

AN:

1489

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000427

Hom.:

Bravo

AF:

0.000234

ExAC

AF:

0.0000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.057

(source)

DANN

Benign

0.58

DEOGEN2

Benign

0.046

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.098

M_CAP

Benign

0.0018

MetaRNN

Benign

0.027

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.69

PhyloP100

-0.56

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.24

REVEL

Benign

0.0060

Sift

Benign

0.18

Sift4G

Benign

0.18

Polyphen

0.0

Vest4

0.065

MVP

0.13

MPC

0.40

ClinPred

0.012

GERP RS

-4.4

Varity_R

0.041

gMVP

0.012

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over