X-136497796-C-G

Variant names:

• chrX-136497796-C-G
• NM_014500.5:c.112C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014500.5(HTATSF1):​c.112C>G​(p.Pro38Ala) 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 25)
• Consequence: HTATSF1 NM_014500.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.797

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.030772597).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTATSF1	NM_014500.5	c.112C>G	p.Pro38Ala	missense_variant	Exon 1 of 9	ENST00000218364.5	NP_055315.2
HTATSF1	NM_001163280.2	c.112C>G	p.Pro38Ala	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.112C>G	p.Pro38Ala	missense_variant	Exon 1 of 9	1	NM_014500.5	ENSP00000218364.4
HTATSF1	ENST00000535601.5	c.112C>G	p.Pro38Ala	missense_variant	Exon 2 of 10	1		ENSP00000442699.1
HTATSF1	ENST00000448450.5	c.112C>G	p.Pro38Ala	missense_variant	Exon 2 of 6	5		ENSP00000411381.1
HTATSF1	ENST00000425695.5	c.112C>G	p.Pro38Ala	missense_variant	Exon 2 of 6	3		ENSP00000412420.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 25

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 27, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.112C>G (p.P38A) alteration is located in exon 2 (coding exon 1) of the HTATSF1 gene. This alteration results from a C to G substitution at nucleotide position 112, causing the proline (P) at amino acid position 38 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.10
DANN	Benign	0.72
DEOGEN2	Benign	0.053	T;T;T;T
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.54	T;T;T;.
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.031	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;.;.;L
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.0	N;N;N;N
REVEL	Benign	0.085
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	0.37	T;T;T;T
Polyphen		0.064	B;.;.;B
Vest4		0.040
MutPred		0.098		Loss of solvent accessibility (P = 0.1322);Loss of solvent accessibility (P = 0.1322);Loss of solvent accessibility (P = 0.1322);Loss of solvent accessibility (P = 0.1322);
MVP		0.28
MPC		0.48
ClinPred		0.047	T
GERP RS		-9.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.031
gMVP		0.35

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-135579955;