Genetic Variant HTATIP2:p.Leu24Trp (chr11-20364308-T-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001098522.2(HTATIP2):c.71T>G(p.Leu24Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

HTATIP2
NM_001098522.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.61

Variant links:

Genes affected

HTATIP2 (HGNC:16637): (HIV-1 Tat interactive protein 2) Enables protein serine/threonine kinase activity. Involved in import into nucleus and regulation of angiogenesis. Acts upstream of or within positive regulation of programmed cell death; positive regulation of transcription by RNA polymerase II; and protein autophosphorylation. Located in cytosol and nuclear envelope. [provided by Alliance of Genome Resources, Apr 2022]

HTATIP2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.818

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTATIP2	NM_001098522.2 link	c.71T>G	p.Leu24Trp	missense_variant	Exon 1 of 5	ENST00000451739.7	NP_001091992.1	Q9BUP3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTATIP2	ENST00000451739.7 link	c.71T>G	p.Leu24Trp	missense_variant	Exon 1 of 5	1	NM_001098522.2	ENSP00000394259.2		Q9BUP3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461522

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727032

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 21, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.173T>G (p.L58W) alteration is located in exon 2 (coding exon 2) of the HTATIP2 gene. This alteration results from a T to G substitution at nucleotide position 173, causing the leucine (L) at amino acid position 58 to be replaced by a tryptophan (W). 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

Pathogenic

0.86

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.16

CADD

Pathogenic

DANN

Benign

0.96

DEOGEN2

Uncertain

0.76

.;D;D;.;D;.;.;.

Eigen

Pathogenic

0.87

Eigen_PC

Pathogenic

0.84

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.91

.;.;.;D;D;.;D;D

M_CAP

Benign

0.039

MetaRNN

Pathogenic

0.82

D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.45

MutationAssessor

Pathogenic

3.3

M;M;M;.;M;M;M;.

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-4.4

D;D;D;D;D;D;D;D

REVEL

Uncertain

0.44

Sift

Uncertain

0.0010

D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.0020

D;D;D;D;D;D;D;D

Polyphen

1.0

D;D;D;D;D;D;D;.

Vest4

0.83

MutPred

0.58

Gain of MoRF binding (P = 0.0266);Gain of MoRF binding (P = 0.0266);Gain of MoRF binding (P = 0.0266);.;Gain of MoRF binding (P = 0.0266);Gain of MoRF binding (P = 0.0266);Gain of MoRF binding (P = 0.0266);Gain of MoRF binding (P = 0.0266);

MVP

0.69

MPC

1.2

ClinPred

1.0

GERP RS

6.0

Varity_R

0.96

gMVP

0.85

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over