Variant rs3824886 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001098522.2(HTATIP2):c.591T>G(p.Ser197Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.909 in 1,613,286 control chromosomes in the GnomAD database, including 677,079 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.83 ( 53818 hom., cov: 28)

Exomes 𝑓: 0.92 ( 623261 hom. )

Consequence

HTATIP2
NM_001098522.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0280

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.832092E-7).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTATIP2	NM_001098522.2 link	c.591T>G	p.Ser197Arg	missense_variant	5/5	ENST00000451739.7	NP_001091992.1	Q9BUP3-1
HTATIP2	NM_001098520.2 link	c.693T>G	p.Ser231Arg	missense_variant	6/6		NP_001091990.1	Q9BUP3-3
HTATIP2	NM_001098521.2 link	c.591T>G	p.Ser197Arg	missense_variant	6/6		NP_001091991.1	Q9BUP3-1
HTATIP2	NM_006410.5 link	c.591T>G	p.Ser197Arg	missense_variant	6/6		NP_006401.3	Q9BUP3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTATIP2	ENST00000451739.7 link	c.591T>G	p.Ser197Arg	missense_variant	5/5	1	NM_001098522.2	ENSP00000394259.2		Q9BUP3-1

Frequencies

GnomAD3 genomes

AF:

0.829

AC:

125628

AN:

151498

Hom.:

53807

Cov.:

show subpopulations

Gnomad AFR

AF:

0.640

Gnomad AMI

AF:

0.959

Gnomad AMR

AF:

0.759

Gnomad ASJ

AF:

0.963

Gnomad EAS

AF:

0.499

Gnomad SAS

AF:

0.884

Gnomad FIN

AF:

0.952

Gnomad MID

AF:

0.927

Gnomad NFE

AF:

0.952

Gnomad OTH

AF:

0.840

GnomAD3 exomes

AF:

0.851

AC:

213765

AN:

251058

Hom.:

93946

AF XY:

0.869

AC XY:

117965

AN XY:

135740

show subpopulations

Gnomad AFR exome

AF:

0.636

Gnomad AMR exome

AF:

0.670

Gnomad ASJ exome

AF:

0.960

Gnomad EAS exome

AF:

0.495

Gnomad SAS exome

AF:

0.902

Gnomad FIN exome

AF:

0.955

Gnomad NFE exome

AF:

0.950

Gnomad OTH exome

AF:

0.890

GnomAD4 exome

AF:

0.918

AC:

1341259

AN:

1461670

Hom.:

623261

Cov.:

AF XY:

0.920

AC XY:

668833

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.628

Gnomad4 AMR exome

AF:

0.679

Gnomad4 ASJ exome

AF:

0.962

Gnomad4 EAS exome

AF:

0.473

Gnomad4 SAS exome

AF:

0.900

Gnomad4 FIN exome

AF:

0.958

Gnomad4 NFE exome

AF:

0.952

Gnomad4 OTH exome

AF:

0.890

GnomAD4 genome

AF:

0.829

AC:

125688

AN:

151616

Hom.:

53818

Cov.:

AF XY:

0.828

AC XY:

61312

AN XY:

74060

show subpopulations

Gnomad4 AFR

AF:

0.640

Gnomad4 AMR

AF:

0.759

Gnomad4 ASJ

AF:

0.963

Gnomad4 EAS

AF:

0.499

Gnomad4 SAS

AF:

0.884

Gnomad4 FIN

AF:

0.952

Gnomad4 NFE

AF:

0.952

Gnomad4 OTH

AF:

0.840

Alfa

AF:

0.903

Hom.:

36153

Bravo

AF:

0.799

TwinsUK

AF:

0.951

AC:

3526

ALSPAC

AF:

0.955

AC:

3682

ESP6500AA

AF:

0.641

AC:

2826

ESP6500EA

AF:

0.950

AC:

8172

ExAC

AF:

0.856

AC:

103934

Asia WGS

AF:

0.726

AC:

2527

AN:

3478

EpiCase

AF:

0.950

EpiControl

AF:

0.950

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.16

T;T;.;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.64

.;.;T;T;T

MetaRNN

Benign

7.8e-7

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.20

N;N;.;N;.

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.48

N;N;N;N;N

REVEL

Benign

0.020

Sift

Benign

0.26

T;T;T;T;T

Sift4G

Benign

0.26

T;T;T;T;T

Polyphen

0.0010

B;B;B;B;.

Vest4

0.081

MutPred

0.41

Gain of catalytic residue at S197 (P = 0.0068);Gain of catalytic residue at S197 (P = 0.0068);.;Gain of catalytic residue at S197 (P = 0.0068);.;

MPC

0.29

ClinPred

0.0045

GERP RS

-5.6

Varity_R

0.34

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over