X-136497805-C-T

Variant names:

• chrX-136497805-C-T
• NM_014500.5:c.121C>T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.11

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]

ACMG classification

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
HTATSF1	NM_014500.5	c.121C>T	p.Leu41Phe	missense_variant	Exon 1 of 9	ENST00000218364.5	NP_055315.2
HTATSF1	NM_001163280.2	c.121C>T	p.Leu41Phe	missense_variant	Exon 2 of 10		NP_001156752.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTATSF1	ENST00000218364.5	c.121C>T	p.Leu41Phe	missense_variant	Exon 1 of 9	1	NM_014500.5	ENSP00000218364.4
HTATSF1	ENST00000535601.5	c.121C>T	p.Leu41Phe	missense_variant	Exon 2 of 10	1		ENSP00000442699.1
HTATSF1	ENST00000448450.5	c.121C>T	p.Leu41Phe	missense_variant	Exon 2 of 6	5		ENSP00000411381.1
HTATSF1	ENST00000425695.5	c.121C>T	p.Leu41Phe	missense_variant	Exon 2 of 6	3		ENSP00000412420.1

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

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;