X-136497805-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_014500.5(HTATSF1):​c.121C>T​(p.Leu41Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Likely benign (★).

Frequency

Genomes: not found (cov: 25)

Consequence

HTATSF1
NM_014500.5 missense

Scores

17

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.11
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.032234788).
BP6
Variant X-136497805-C-T is Benign according to our data. Variant chrX-136497805-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3527072.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HTATSF1NM_014500.5 linkc.121C>T p.Leu41Phe missense_variant Exon 1 of 9 ENST00000218364.5 NP_055315.2 O43719
HTATSF1NM_001163280.2 linkc.121C>T p.Leu41Phe missense_variant Exon 2 of 10 NP_001156752.1 O43719

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HTATSF1ENST00000218364.5 linkc.121C>T p.Leu41Phe missense_variant Exon 1 of 9 1 NM_014500.5 ENSP00000218364.4 O43719
HTATSF1ENST00000535601.5 linkc.121C>T p.Leu41Phe missense_variant Exon 2 of 10 1 ENSP00000442699.1 O43719
HTATSF1ENST00000448450.5 linkc.121C>T p.Leu41Phe missense_variant Exon 2 of 6 5 ENSP00000411381.1 Q5H918
HTATSF1ENST00000425695.5 linkc.121C>T p.Leu41Phe missense_variant Exon 2 of 6 3 ENSP00000412420.1 Q5H919

Frequencies

GnomAD3 genomes
Cov.:
25
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
25

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Sep 27, 2024
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.053
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.77
CADD
Benign
7.3
DANN
Benign
0.93
DEOGEN2
Benign
0.031
T;T;T;T
FATHMM_MKL
Benign
0.0062
N
LIST_S2
Benign
0.56
T;T;T;.
M_CAP
Benign
0.0048
T
MetaRNN
Benign
0.032
T;T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
-1.5
N;.;.;N
PrimateAI
Benign
0.30
T
PROVEAN
Benign
1.3
N;N;N;N
REVEL
Benign
0.032
Sift
Benign
1.0
T;T;T;T
Sift4G
Benign
1.0
T;T;T;T
Polyphen
0.0
B;.;.;B
Vest4
0.072
MutPred
0.21
Loss of catalytic residue at L41 (P = 0.1106);Loss of catalytic residue at L41 (P = 0.1106);Loss of catalytic residue at L41 (P = 0.1106);Loss of catalytic residue at L41 (P = 0.1106);
MVP
0.23
MPC
0.54
ClinPred
0.078
T
GERP RS
0.14
Varity_R
0.057
gMVP
0.26

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.

Other links and lift over

hg19: chrX-135579964; API