Genetic Variant NM_001098522.2:c.253C>G (chr11-20367231-C-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001098522.2(HTATIP2):c.253C>G(p.His85Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,812 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. H85Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

HTATIP2
NM_001098522.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.41

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098522.2. 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.253C>G	p.His85Asp	missense	Exon 2 of 5	NP_001091992.1	Q9BUP3-1
HTATIP2	NM_001098520.2		c.355C>G	p.His119Asp	missense	Exon 3 of 6	NP_001091990.1	Q9BUP3-3
HTATIP2	NM_001098521.2		c.253C>G	p.His85Asp	missense	Exon 3 of 6	NP_001091991.1	Q9BUP3-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HTATIP2	ENST00000451739.7	TSL:1 MANE Select	c.253C>G	p.His85Asp	missense	Exon 2 of 5	ENSP00000394259.2	Q9BUP3-1
HTATIP2	ENST00000532081.1	TSL:1	c.253C>G	p.His85Asp	missense	Exon 2 of 2	ENSP00000432107.1	Q9BUP3-2
HTATIP2	ENST00000419348.6	TSL:2	c.355C>G	p.His119Asp	missense	Exon 3 of 6	ENSP00000392985.2	Q9BUP3-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461812

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727196

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:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86204

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:

1111994

Other (OTH)

AF:

0.0000166

AC:

AN:

60394

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

Pathogenic

0.77

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.34

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Benign

0.69

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.0095

MetaRNN

Uncertain

0.66

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

PhyloP100

4.4

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-4.4

REVEL

Benign

0.22

Sift

Benign

0.095

Sift4G

Benign

0.20

Polyphen

1.0

Vest4

0.77

MutPred

0.53

Gain of helix (P = 0.2684)

MVP

0.59

MPC

1.0

ClinPred

0.99

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.93

gMVP

0.88

Mutation Taster

=32/68

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.55

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.55

Position offset: -3

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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