chr11-20382178-G-A

Variant names:

• chr11-20382178-G-A
• rs747806383
• NM_001098522.2:c.442G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001098522.2(HTATIP2):​c.442G>A​(p.Gly148Arg) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00011 in 1,571,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: HTATIP2 NM_001098522.2 missense, splice_region
• Scores: Splicing: ADA: 0.9969
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.47
• 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 1 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

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.442G>A	p.Gly148Arg	missense splice_region	Exon 4 of 5	NP_001091992.1	Q9BUP3-1
	HTATIP2	NM_001098520.2		c.544G>A	p.Gly182Arg	missense splice_region	Exon 5 of 6	NP_001091990.1	Q9BUP3-3
	HTATIP2	NM_001098521.2		c.442G>A	p.Gly148Arg	missense splice_region	Exon 5 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.442G>A	p.Gly148Arg	missense splice_region	Exon 4 of 5	ENSP00000394259.2	Q9BUP3-1
	HTATIP2	ENST00000419348.6	TSL:2	c.544G>A	p.Gly182Arg	missense splice_region	Exon 5 of 6	ENSP00000392985.2	Q9BUP3-3
	HTATIP2	ENST00000421577.6	TSL:2	c.442G>A	p.Gly148Arg	missense splice_region	Exon 5 of 6	ENSP00000397752.2	Q9BUP3-1

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152174 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000877 AC: 22 AN: 250910 AF XY: 0.000111

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000185

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000118 AC: 167 AN: 1418898 Hom.: 0 Cov.: 26 AF XY: 0.000109 AC XY: 77 AN XY: 708736

African (AFR) AF: 0.00 AC: 0 AN: 32684

American (AMR) AF: 0.00 AC: 0 AN: 44604

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25846

East Asian (EAS) AF: 0.00 AC: 0 AN: 39498

South Asian (SAS) AF: 0.00 AC: 0 AN: 85214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5706

European-Non Finnish (NFE) AF: 0.000146 AC: 157 AN: 1073014

Other (OTH) AF: 0.000170 AC: 10 AN: 58958

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152174 Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4 AN XY: 74344

African (AFR) AF: 0.00 AC: 0 AN: 41442

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000115 Hom.: 0

Bravo AF: 0.0000529

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.000132 AC: 16

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

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	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	34
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.45	T
Eigen	Pathogenic	0.95
Eigen_PC	Pathogenic	0.89
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-0.45	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		7.5
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-7.4	D
REVEL	Uncertain	0.57
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.95
MutPred		0.74		Gain of methylation at K147 (P = 0.05)
MVP		0.70
MPC		1.0
ClinPred		0.96	D
GERP RS		5.6
Varity_R		0.98
gMVP		0.92
Mutation Taster		=9/91	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.93
SpliceAI score (max)		0.070		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: rs747806383; hg19: chr11-20403724;