Genetic Variant ENST00000532081.1:c.302C>A (chr11-20367280-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000532081.1(HTATIP2):c.302C>A(p.Ala101Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. A101V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

HTATIP2
ENST00000532081.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.68

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30180287).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000532081.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HTATIP2	NM_001098522.2	MANE Select	c.302C>A	p.Ala101Glu	missense splice_region	Exon 2 of 5	NP_001091992.1	Q9BUP3-1
HTATIP2	NM_001098523.2		c.302C>A	p.Ala101Glu	missense	Exon 2 of 2	NP_001091993.1	Q9BUP3-2
HTATIP2	NM_001098520.2		c.404C>A	p.Ala135Glu	missense splice_region	Exon 3 of 6	NP_001091990.1	Q9BUP3-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HTATIP2	ENST00000532081.1	TSL:1	c.302C>A	p.Ala101Glu	missense	Exon 2 of 2	ENSP00000432107.1	Q9BUP3-2
HTATIP2	ENST00000451739.7	TSL:1 MANE Select	c.302C>A	p.Ala101Glu	missense splice_region	Exon 2 of 5	ENSP00000394259.2	Q9BUP3-1
HTATIP2	ENST00000530266.5	TSL:3	c.302C>A	p.Ala101Glu	missense	Exon 3 of 3	ENSP00000436548.1	Q9BUP3-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461686

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727114

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26088

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86132

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111992

Other (OTH)

AF:

0.00

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

Eigen

Benign

0.093

Eigen_PC

Benign

0.18

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.80

M_CAP

Benign

0.018

MetaRNN

Benign

0.25

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

2.7

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.2

REVEL

Benign

0.084

Sift

Uncertain

0.016

Sift4G

Uncertain

0.0040

Polyphen

0.73

Vest4

0.16

MutPred

0.57

Gain of disorder (P = 0.0349)

MVP

0.61

MPC

0.35

ClinPred

0.79

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.57

gMVP

0.67

Mutation Taster

=40/60

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over