chrX-136499613-A-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_014500.5(HTATSF1):​c.202A>C​(p.Ile68Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000358 in 111,597 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000036 (0 hom., 2 hem., cov: 23)
  • Exomes 𝑓: 9.5e-7 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: HTATSF1 NM_014500.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Hemizygotes in GnomAd4 at 2 gene

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>C	p.Ile68Leu	missense	Exon 2 of 9	NP_055315.2
	HTATSF1	NM_001163280.2		c.202A>C	p.Ile68Leu	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>C	p.Ile68Leu	missense	Exon 2 of 9	ENSP00000218364.4	O43719
	HTATSF1	ENST00000535601.5	TSL:1	c.202A>C	p.Ile68Leu	missense	Exon 3 of 10	ENSP00000442699.1	O43719
	HTATSF1	ENST00000866998.1		c.202A>C	p.Ile68Leu	missense	Exon 2 of 9	ENSP00000537057.1

Frequencies

GnomAD3 genomes AF: 0.0000358 AC: 4 AN: 111597 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000654

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000377

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000693 AC: 1 AN: 144331 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000144

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.45e-7 AC: 1 AN: 1057765 Hom.: 0 Cov.: 27 AF XY: 0.00000294 AC XY: 1 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 AF: 0.0000358 AC: 4 AN: 111597 Hom.: 0 Cov.: 23 AF XY: 0.0000590 AC XY: 2 AN XY: 33879

African (AFR) AF: 0.0000654 AC: 2 AN: 30577

American (AMR) AF: 0.00 AC: 0 AN: 10543

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2638

East Asian (EAS) AF: 0.00 AC: 0 AN: 3594

South Asian (SAS) AF: 0.00 AC: 0 AN: 2655

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6065

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.0000377 AC: 2 AN: 53096

Other (OTH) AF: 0.00 AC: 0 AN: 1505

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	22
DANN	Benign	0.75
DEOGEN2	Benign	0.042	T
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.4
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.023
Sift	Benign	0.18	T
Sift4G	Benign	0.68	T
Polyphen		0.11	B
Vest4		0.24
MutPred		0.44		Loss of sheet (P = 0.0011)
MVP		0.51
MPC		0.54
ClinPred		0.59	D
GERP RS		4.5
Varity_R		0.23
gMVP		0.49
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.26		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.26		Position offset: 15

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs889857618; hg19: chrX-135581772;