chr11-20383113-A-G

Variant names:

• chr11-20383113-A-G
• rs1321321475
• NM_001098522.2:c.637A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001098522.2(HTATIP2):​c.637A>G​(p.Asn213Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. N213H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: HTATIP2 NM_001098522.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.38
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36844838).

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.637A>G	p.Asn213Asp	missense	Exon 5 of 5	NP_001091992.1	Q9BUP3-1
	HTATIP2	NM_001098520.2		c.739A>G	p.Asn247Asp	missense	Exon 6 of 6	NP_001091990.1	Q9BUP3-3
	HTATIP2	NM_001098521.2		c.637A>G	p.Asn213Asp	missense	Exon 6 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.637A>G	p.Asn213Asp	missense	Exon 5 of 5	ENSP00000394259.2	Q9BUP3-1
	HTATIP2	ENST00000419348.6	TSL:2	c.739A>G	p.Asn247Asp	missense	Exon 6 of 6	ENSP00000392985.2	Q9BUP3-3
	HTATIP2	ENST00000421577.6	TSL:2	c.637A>G	p.Asn213Asp	missense	Exon 6 of 6	ENSP00000397752.2	Q9BUP3-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461864 Hom.: 0 Cov.: 38 AF XY: 0.00000138 AC XY: 1 AN XY: 727224

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112004

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.039
Eigen_PC	Benign	-0.022
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		4.4
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.21
Sift	Benign	0.12	T
Sift4G	Benign	0.64	T
Polyphen		0.71	P
Vest4		0.51
MutPred		0.69		Loss of MoRF binding (P = 0.0432)
MVP		0.43
MPC		0.90
ClinPred		0.79	D
GERP RS		2.5
Varity_R		0.38
gMVP		0.86
Mutation Taster		=73/27	polymorphism

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: rs1321321475; hg19: chr11-20404659;