X-136499613-A-G

Variant names:

• chrX-136499613-A-G
• rs889857618
• NM_014500.5:c.202A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014500.5(HTATSF1):​c.202A>G​(p.Ile68Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000945 in 1,057,765 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. 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. I68L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.5e-7 (0 hom. 0 hem.)
• Consequence: HTATSF1 NM_014500.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.44
• Publications: 0 publications found

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

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=0.2037299).

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.202A>G	p.Ile68Val	missense	Exon 2 of 9	NP_055315.2
	HTATSF1	NM_001163280.2		c.202A>G	p.Ile68Val	missense	Exon 3 of 10	NP_001156752.1	O43719

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTATSF1	ENST00000218364.5	TSL:1 MANE Select	c.202A>G	p.Ile68Val	missense	Exon 2 of 9	ENSP00000218364.4	O43719
	HTATSF1	ENST00000535601.5	TSL:1	c.202A>G	p.Ile68Val	missense	Exon 3 of 10	ENSP00000442699.1	O43719
	HTATSF1	ENST00000866998.1		c.202A>G	p.Ile68Val	missense	Exon 2 of 9	ENSP00000537057.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.45e-7 AC: 1 AN: 1057765 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 339567

African (AFR) AF: 0.00 AC: 0 AN: 24241

American (AMR) AF: 0.00 AC: 0 AN: 25189

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17498

East Asian (EAS) AF: 0.00 AC: 0 AN: 29175

South Asian (SAS) AF: 0.00 AC: 0 AN: 47099

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39653

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3972

European-Non Finnish (NFE) AF: 0.00000121 AC: 1 AN: 826713

Other (OTH) AF: 0.00 AC: 0 AN: 44225

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.070	T
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		2.4
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.75	N
REVEL	Benign	0.062
Sift	Uncertain	0.029	D
Sift4G	Uncertain	0.033	D
Polyphen		0.96	D
Vest4		0.27
MutPred		0.42		Loss of sheet (P = 0.0025)
MVP		0.57
MPC		0.65
ClinPred		0.77	D
GERP RS		4.5
Varity_R		0.19
gMVP		0.36
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs889857618; hg19: chrX-135581772;