chr11-20364422-A-G

Variant names:

• chr11-20364422-A-G
• rs1261792959
• NM_001098522.2:c.185A>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001098522.2(HTATIP2):​c.185A>G​(p.Tyr62Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000481 in 1,454,880 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Y62S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: HTATIP2 NM_001098522.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.41
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.75

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.185A>G	p.Tyr62Cys	missense	Exon 1 of 5	NP_001091992.1	Q9BUP3-1
	HTATIP2	NM_001098520.2		c.287A>G	p.Tyr96Cys	missense	Exon 2 of 6	NP_001091990.1	Q9BUP3-3
	HTATIP2	NM_001098521.2		c.185A>G	p.Tyr62Cys	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.185A>G	p.Tyr62Cys	missense	Exon 1 of 5	ENSP00000394259.2	Q9BUP3-1
	HTATIP2	ENST00000532081.1	TSL:1	c.185A>G	p.Tyr62Cys	missense	Exon 1 of 2	ENSP00000432107.1	Q9BUP3-2
	HTATIP2	ENST00000419348.6	TSL:2	c.287A>G	p.Tyr96Cys	missense	Exon 2 of 6	ENSP00000392985.2	Q9BUP3-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000481 AC: 7 AN: 1454880 Hom.: 0 Cov.: 32 AF XY: 0.00000415 AC XY: 3 AN XY: 723088

African (AFR) AF: 0.00 AC: 0 AN: 33158

American (AMR) AF: 0.00 AC: 0 AN: 43792

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25886

East Asian (EAS) AF: 0.00 AC: 0 AN: 39522

South Asian (SAS) AF: 0.00 AC: 0 AN: 85854

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53322

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 0.00000632 AC: 7 AN: 1107566

Other (OTH) AF: 0.00 AC: 0 AN: 60048

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.061	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.018	T
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-0.69	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		5.4
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.28
Sift	Benign	0.033	D
Sift4G	Uncertain	0.042	D
Polyphen		1.0	D
Vest4		0.79
MutPred		0.41		Gain of methylation at K63 (P = 0.0207)
MVP		0.70
MPC		1.0
ClinPred		0.99	D
GERP RS		6.0
PromoterAI		0.0032	Neutral
Varity_R		0.74
gMVP		0.63
Mutation Taster		=40/60	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: rs1261792959; hg19: chr11-20385968;