chrX-136497803-C-T

Variant names:

• chrX-136497803-C-T
• rs1447318632
• NM_014500.5:c.119C>T

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.119C>T​(p.Ser40Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000417 in 1,198,770 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 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., 0 hem., cov: 24)
  • Exomes 𝑓: 9.2e-7 (0 hom. 1 hem.)
• Consequence: HTATSF1 NM_014500.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.86
• 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=0.21583834).

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.119C>T	p.Ser40Phe	missense	Exon 1 of 9	NP_055315.2
	HTATSF1	NM_001163280.2		c.119C>T	p.Ser40Phe	missense	Exon 2 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.119C>T	p.Ser40Phe	missense	Exon 1 of 9	ENSP00000218364.4	O43719
	HTATSF1	ENST00000535601.5	TSL:1	c.119C>T	p.Ser40Phe	missense	Exon 2 of 10	ENSP00000442699.1	O43719
	HTATSF1	ENST00000866998.1		c.119C>T	p.Ser40Phe	missense	Exon 1 of 9	ENSP00000537057.1

Frequencies

GnomAD3 genomes AF: 0.0000356 AC: 4 AN: 112398 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000278

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: 0.00

Gnomad OTH AF: 0.000664

GnomAD4 exome AF: 9.20e-7 AC: 1 AN: 1086372 Hom.: 0 Cov.: 29 AF XY: 0.00000282 AC XY: 1 AN XY: 354224

African (AFR) AF: 0.0000382 AC: 1 AN: 26159

American (AMR) AF: 0.00 AC: 0 AN: 34849

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19123

East Asian (EAS) AF: 0.00 AC: 0 AN: 29703

South Asian (SAS) AF: 0.00 AC: 0 AN: 52937

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40133

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4070

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 834022

Other (OTH) AF: 0.00 AC: 0 AN: 45376

GnomAD4 genome AF: 0.0000356 AC: 4 AN: 112398 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 34544

African (AFR) AF: 0.00 AC: 0 AN: 30923

American (AMR) AF: 0.000278 AC: 3 AN: 10777

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2658

East Asian (EAS) AF: 0.00 AC: 0 AN: 3557

South Asian (SAS) AF: 0.00 AC: 0 AN: 2719

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6144

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53195

Other (OTH) AF: 0.000664 AC: 1 AN: 1506

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000567

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	0.12
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		4.9
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.095
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.018	D
Polyphen		1.0	D
Vest4		0.27
MutPred		0.17		Loss of glycosylation at S40 (P = 0.0076)
MVP		0.44
MPC		1.3
ClinPred		0.95	D
GERP RS		4.5
PromoterAI		0.0026	Neutral
Varity_R		0.29
gMVP		0.54
Mutation Taster		=97/3	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: rs1447318632; hg19: chrX-135579962;