Genetic Variant NM_014500.5:c.22G>A (chrX-136497706-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014500.5(HTATSF1):c.22G>A(p.Gly8Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000184 in 1,084,455 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.0000018 ( 0 hom. 0 hem. )

Consequence

HTATSF1
NM_014500.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.66

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07465628).

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.22G>A	p.Gly8Arg	missense	Exon 1 of 9	NP_055315.2
	HTATSF1	NM_001163280.2		c.22G>A	p.Gly8Arg	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.22G>A	p.Gly8Arg	missense	Exon 1 of 9	ENSP00000218364.4	O43719
HTATSF1	ENST00000535601.5	TSL:1	c.22G>A	p.Gly8Arg	missense	Exon 2 of 10	ENSP00000442699.1	O43719
HTATSF1	ENST00000866998.1		c.22G>A	p.Gly8Arg	missense	Exon 1 of 9	ENSP00000537057.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000566

AC:

AN:

176679

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.000231

GnomAD4 exome

AF:

0.00000184

AC:

AN:

1084455

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

352863

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26194

American (AMR)

AF:

0.00

AC:

AN:

34769

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19058

East Asian (EAS)

AF:

0.00

AC:

AN:

29776

South Asian (SAS)

AF:

0.00

AC:

AN:

52846

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40168

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4072

European-Non Finnish (NFE)

AF:

0.00000120

AC:

AN:

832215

Other (OTH)

AF:

0.0000220

AC:

AN:

45357

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

Cov.:

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

0.11

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.060

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.67

M_CAP

Benign

0.0074

MetaRNN

Benign

0.075

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

PhyloP100

1.7

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.3

REVEL

Benign

0.14

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.013

Polyphen

0.54

Vest4

0.051

MutPred

0.11

Gain of helix (P = 0.0696)

MVP

0.45

MPC

0.62

ClinPred

0.23

GERP RS

-1.6

PromoterAI

-0.020

Neutral

(source)

Varity_R

0.16

gMVP

0.52

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over