rs3824886

Variant names:

• chr11-20383067-T-G
• rs3824886
• NM_001098522.2:c.591T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.83 (53818 hom., cov: 28)
  • Exomes 𝑓: 0.92 (623261 hom.)
• Consequence: HTATIP2 NM_001098522.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0280
• Publications: 37 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HTATIP2	NM_001098522.2	c.591T>G	p.Ser197Arg	missense_variant	Exon 5 of 5	ENST00000451739.7	NP_001091992.1
HTATIP2	NM_001098520.2	c.693T>G	p.Ser231Arg	missense_variant	Exon 6 of 6		NP_001091990.1
HTATIP2	NM_001098521.2	c.591T>G	p.Ser197Arg	missense_variant	Exon 6 of 6		NP_001091991.1
HTATIP2	NM_006410.5	c.591T>G	p.Ser197Arg	missense_variant	Exon 6 of 6		NP_006401.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTATIP2	ENST00000451739.7	c.591T>G	p.Ser197Arg	missense_variant	Exon 5 of 5	1	NM_001098522.2	ENSP00000394259.2

Frequencies

GnomAD3 genomes AF: 0.829 AC: 125628 AN: 151498 Hom.: 53807 Cov.: 28

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

GnomAD2 exomes AF: 0.851 AC: 213765 AN: 251058 AF XY: 0.869

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 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.: 50 AF XY: 0.920 AC XY: 668833 AN XY: 727152

African (AFR) AF: 0.628 AC: 21017 AN: 33470

American (AMR) AF: 0.679 AC: 30338 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.962 AC: 25147 AN: 26136

East Asian (EAS) AF: 0.473 AC: 18774 AN: 39684

South Asian (SAS) AF: 0.900 AC: 77613 AN: 86248

European-Finnish (FIN) AF: 0.958 AC: 51172 AN: 53414

Middle Eastern (MID) AF: 0.923 AC: 5321 AN: 5766

European-Non Finnish (NFE) AF: 0.952 AC: 1058132 AN: 1111912

Other (OTH) AF: 0.890 AC: 53745 AN: 60390

GnomAD4 genome AF: 0.829 AC: 125688 AN: 151616 Hom.: 53818 Cov.: 28 AF XY: 0.828 AC XY: 61312 AN XY: 74060

African (AFR) AF: 0.640 AC: 26384 AN: 41220

American (AMR) AF: 0.759 AC: 11545 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.963 AC: 3340 AN: 3468

East Asian (EAS) AF: 0.499 AC: 2545 AN: 5096

South Asian (SAS) AF: 0.884 AC: 4253 AN: 4810

European-Finnish (FIN) AF: 0.952 AC: 10028 AN: 10538

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.952 AC: 64685 AN: 67960

Other (OTH) AF: 0.840 AC: 1762 AN: 2098

Alfa AF: 0.866 Hom.: 49082

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	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	10
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	N
LIST_S2	Benign	0.64	.;.;T;T;T
MetaRNN	Benign	7.8e-7	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.20	N;N;.;N;.
PhyloP100		-0.028
PrimateAI	Benign	0.37	T
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	T
GERP RS		-5.6
Varity_R		0.34
gMVP		0.52
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3824886; hg19: chr11-20404613; COSMIC: COSV58178278; COSMIC: COSV58178278;