chr11-20364385-A-T

Variant names:

• chr11-20364385-A-T
• rs200473579
• NM_001098522.2:c.148A>T

Variant summary

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

The NM_001098522.2(HTATIP2):​c.148A>T​(p.Ile50Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,430 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. I50T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: HTATIP2 NM_001098522.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.67
• Publications: 2 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.148A>T	p.Ile50Phe	missense	Exon 1 of 5	NP_001091992.1	Q9BUP3-1
	HTATIP2	NM_001098520.2		c.250A>T	p.Ile84Phe	missense	Exon 2 of 6	NP_001091990.1	Q9BUP3-3
	HTATIP2	NM_001098521.2		c.148A>T	p.Ile50Phe	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.148A>T	p.Ile50Phe	missense	Exon 1 of 5	ENSP00000394259.2	Q9BUP3-1
	HTATIP2	ENST00000532081.1	TSL:1	c.148A>T	p.Ile50Phe	missense	Exon 1 of 2	ENSP00000432107.1	Q9BUP3-2
	HTATIP2	ENST00000419348.6	TSL:2	c.250A>T	p.Ile84Phe	missense	Exon 2 of 6	ENSP00000392985.2	Q9BUP3-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459430 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 725708

African (AFR) AF: 0.00 AC: 0 AN: 33428

American (AMR) AF: 0.00 AC: 0 AN: 44508

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39612

South Asian (SAS) AF: 0.00 AC: 0 AN: 86092

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110266

Other (OTH) AF: 0.00 AC: 0 AN: 60268

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	T
Eigen	Uncertain	0.66
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0065	T
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.7	L
PhyloP100		7.7
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.32
Sift	Benign	0.17	T
Sift4G	Benign	0.15	T
Polyphen		1.0	D
Vest4		0.88
MutPred		0.54		Loss of catalytic residue at L55 (P = 0.0474)
MVP		0.56
MPC		1.2
ClinPred		0.98	D
GERP RS		6.0
PromoterAI		-0.030	Neutral
Varity_R		0.90
gMVP		0.78
Mutation Taster		=26/74	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: rs200473579; hg19: chr11-20385931;