11-20364328-G-T

Variant names:

• chr11-20364328-G-T
• rs527767104
• NM_001098522.2:c.91G>T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001098522.2(HTATIP2):​c.91G>T​(p.Gly31Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. G31R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: HTATIP2 NM_001098522.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.22
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.978

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTATIP2	NM_001098522.2	MANE Select	c.91G>T	p.Gly31Cys	missense	Exon 1 of 5	NP_001091992.1	Q9BUP3-1
	HTATIP2	NM_001098520.2		c.193G>T	p.Gly65Cys	missense	Exon 2 of 6	NP_001091990.1	Q9BUP3-3
	HTATIP2	NM_001098521.2		c.91G>T	p.Gly31Cys	missense	Exon 2 of 6	NP_001091991.1	Q9BUP3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTATIP2	ENST00000451739.7	TSL:1 MANE Select	c.91G>T	p.Gly31Cys	missense	Exon 1 of 5	ENSP00000394259.2	Q9BUP3-1
	HTATIP2	ENST00000532081.1	TSL:1	c.91G>T	p.Gly31Cys	missense	Exon 1 of 2	ENSP00000432107.1	Q9BUP3-2
	HTATIP2	ENST00000419348.6	TSL:2	c.193G>T	p.Gly65Cys	missense	Exon 2 of 6	ENSP00000392985.2	Q9BUP3-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.48	D
BayesDel_noAF	Pathogenic	0.45
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.67	D
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.98
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.18	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Pathogenic	4.5	H
PhyloP100		8.2
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-8.5	D
REVEL	Pathogenic	0.90
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.97
MutPred		0.85		Loss of methylation at R32 (P = 0.0643)
MVP		0.98
MPC		0.94
ClinPred		1.0	D
GERP RS		6.0
PromoterAI		-0.15	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.99
gMVP		0.92
Mutation Taster		=15/85	disease causing

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

Other links and lift over

dbSNP: rs527767104; hg19: chr11-20385874;