11-20363827-G-T

Variant names:

• chr11-20363827-G-T
• NM_001098522.2:c.-411G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001098520.2(HTATIP2):​c.16G>T​(p.Ala6Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000914 in 1,093,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 9.1e-7 (0 hom.)
• Consequence: HTATIP2 NM_001098520.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.05
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16416624).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098520.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTATIP2	NM_001098522.2	MANE Select	c.-411G>T		5_prime_UTR	Exon 1 of 5	NP_001091992.1	Q9BUP3-1
	HTATIP2	NM_001098520.2		c.16G>T	p.Ala6Ser	missense	Exon 1 of 6	NP_001091990.1	Q9BUP3-3
	HTATIP2	NM_001098523.2		c.-411G>T		5_prime_UTR	Exon 1 of 2	NP_001091993.1	Q9BUP3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTATIP2	ENST00000451739.7	TSL:1 MANE Select	c.-411G>T		5_prime_UTR	Exon 1 of 5	ENSP00000394259.2	Q9BUP3-1
	HTATIP2	ENST00000419348.6	TSL:2	c.16G>T	p.Ala6Ser	missense	Exon 1 of 6	ENSP00000392985.2	Q9BUP3-3
	HTATIP2	ENST00000421577.6	TSL:2	c.-2+78G>T		intron	N/A	ENSP00000397752.2	Q9BUP3-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 9.14e-7 AC: 1 AN: 1093806 Hom.: 0 Cov.: 30 AF XY: 0.00000193 AC XY: 1 AN XY: 517696

African (AFR) AF: 0.00 AC: 0 AN: 22988

American (AMR) AF: 0.00 AC: 0 AN: 8448

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14378

East Asian (EAS) AF: 0.00 AC: 0 AN: 26604

South Asian (SAS) AF: 0.00 AC: 0 AN: 20208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31236

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3446

European-Non Finnish (NFE) AF: 0.00000108 AC: 1 AN: 922654

Other (OTH) AF: 0.00 AC: 0 AN: 43844

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	14
DANN	Benign	0.95
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.30	T
M_CAP	Pathogenic	0.30	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.96	T
PhyloP100		2.1
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	0.050	N
REVEL	Benign	0.063
Sift	Benign	0.046	D
Sift4G	Benign	0.23	T
Polyphen		0.081	B
Vest4		0.21
MutPred		0.17		Gain of glycosylation at A6 (P = 0.0012)
MVP		0.56
MPC		0.54
ClinPred		0.87	D
GERP RS		3.6
PromoterAI		0.084	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.36
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

hg19: chr11-20385373;