dbSNP rs1156538917: HTATSF1:p.Gln31Lys (chrX-136497775-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -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. 14/20 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

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTATSF1	NM_014500.5 link	c.91C>A	p.Gln31Lys	missense_variant	Exon 1 of 9	ENST00000218364.5	NP_055315.2	O43719
HTATSF1	NM_001163280.2 link	c.91C>A	p.Gln31Lys	missense_variant	Exon 2 of 10		NP_001156752.1	O43719

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HTATSF1	ENST00000218364.5 link	c.91C>A	p.Gln31Lys	missense_variant	Exon 1 of 9	1	NM_014500.5	ENSP00000218364.4	O43719
HTATSF1	ENST00000535601.5 link	c.91C>A	p.Gln31Lys	missense_variant	Exon 2 of 10	1		ENSP00000442699.1	O43719
HTATSF1	ENST00000448450.5 link	c.91C>A	p.Gln31Lys	missense_variant	Exon 2 of 6	5		ENSP00000411381.1	Q5H918
HTATSF1	ENST00000425695.5 link	c.91C>A	p.Gln31Lys	missense_variant	Exon 2 of 6	3		ENSP00000412420.1	Q5H919

Frequencies

GnomAD3 genomes

AF:

0.00000889

AC:

AN:

112485

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34647

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

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000925

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:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.75

CADD

Benign

9.4

DANN

Benign

0.84

DEOGEN2

Benign

0.083

T;T;T;T

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.71

T;T;T;.

M_CAP

Benign

0.0053

MetaRNN

Benign

0.052

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;.;.;L

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.99

N;N;N;N

REVEL

Benign

0.012

Sift

Uncertain

0.020

D;T;T;D

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.087

B;.;.;B

Vest4

0.078

MutPred

0.20

Gain of ubiquitination at Q31 (P = 0.0016);Gain of ubiquitination at Q31 (P = 0.0016);Gain of ubiquitination at Q31 (P = 0.0016);Gain of ubiquitination at Q31 (P = 0.0016);

MVP

0.29

MPC

0.64

ClinPred

0.091

GERP RS

1.9

Varity_R

0.21

gMVP

0.57

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over