Genetic Variant NM_014500.5:c.91C>A (chrX-136497775-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014500.5(HTATSF1):c.91C>A(p.Gln31Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 112,537 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q31E) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 24)

Consequence

HTATSF1
NM_014500.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00900

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05215171).

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.91C>A	p.Gln31Lys	missense	Exon 1 of 9	NP_055315.2
	HTATSF1	NM_001163280.2		c.91C>A	p.Gln31Lys	missense	Exon 2 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.91C>A	p.Gln31Lys	missense	Exon 1 of 9	ENSP00000218364.4	O43719
HTATSF1	ENST00000535601.5	TSL:1	c.91C>A	p.Gln31Lys	missense	Exon 2 of 10	ENSP00000442699.1	O43719
HTATSF1	ENST00000866998.1		c.91C>A	p.Gln31Lys	missense	Exon 1 of 9	ENSP00000537057.1

Frequencies

GnomAD3 genomes

AF:

0.00000889

AC:

AN:

112485

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000927

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:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000889

AC:

AN:

112537

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34709

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

31049

American (AMR)

AF:

0.0000925

AC:

AN:

10805

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2651

East Asian (EAS)

AF:

0.00

AC:

AN:

3563

South Asian (SAS)

AF:

0.00

AC:

AN:

2709

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6166

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53167

Other (OTH)

AF:

0.00

AC:

AN:

1525

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.75

CADD

Benign

9.4

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.083

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.71

M_CAP

Benign

0.0053

MetaRNN

Benign

0.052

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

PhyloP100

-0.0090

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.99

REVEL

Benign

0.012

Sift

Uncertain

0.020

Sift4G

Benign

1.0

Polyphen

0.087

Vest4

0.078

MutPred

0.20

Gain of ubiquitination at Q31 (P = 0.0016)

MVP

0.29

MPC

0.64

ClinPred

0.091

GERP RS

1.9

PromoterAI

0.039

Neutral

(source)

Varity_R

0.21

gMVP

0.57

Mutation Taster

=96/4

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over