rs766005493

Variant names:

• chr1-11747484-C-T
• rs766005493
• NM_020350.5:c.107C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_020350.5(AGTRAP):​c.107C>T​(p.Thr36Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,614,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: AGTRAP NM_020350.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.46
• Publications: 0 publications found

Genes affected

AGTRAP (HGNC:13539): (angiotensin II receptor associated protein) This gene encodes a transmembrane protein localized to the plasma membrane and perinuclear vesicular structures. The gene product interacts with the angiotensin II type I receptor and negatively regulates angiotensin II signaling. Alternative splicing of this gene generates multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.23145282).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020350.5. 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
	AGTRAP	NM_020350.5	MANE Select	c.107C>T	p.Thr36Ile	missense	Exon 3 of 5	NP_065083.3
	AGTRAP	NM_001040194.2		c.107C>T	p.Thr36Ile	missense	Exon 3 of 5	NP_001035284.1	Q6RW13-2
	AGTRAP	NM_001040196.2		c.204C>T	p.His68His	synonymous	Exon 4 of 6	NP_001035286.1	Q6RW13-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGTRAP	ENST00000314340.10	TSL:1 MANE Select	c.107C>T	p.Thr36Ile	missense	Exon 3 of 5	ENSP00000319713.5	Q6RW13-1
	AGTRAP	ENST00000376629.8	TSL:1	c.107C>T	p.Thr36Ile	missense	Exon 3 of 5	ENSP00000365816.4	Q6RW13-2
	AGTRAP	ENST00000856550.1		c.143C>T	p.Thr48Ile	missense	Exon 4 of 6	ENSP00000526609.1

Frequencies

GnomAD3 genomes AF: 0.0000328 AC: 5 AN: 152254 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000107 AC: 27 AN: 251340 AF XY: 0.0000883

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00141

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000164 AC: 24 AN: 1461840 Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10 AN XY: 727220

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

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

East Asian (EAS) AF: 0.000453 AC: 18 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111984

Other (OTH) AF: 0.0000497 AC: 3 AN: 60390

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152254 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74388

African (AFR) AF: 0.0000241 AC: 1 AN: 41468

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000769 AC: 4 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000416

ExAC AF: 0.000107 AC: 13

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	0.71
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.069	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		1.5
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.25
Sift	Benign	0.042	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.98	D
Vest4		0.47
MutPred		0.71		Loss of glycosylation at T36 (P = 0.146)
MVP		0.60
MPC		0.84
ClinPred		0.22	T
GERP RS		4.2
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		3.7
Varity_R		0.11
gMVP		0.80
Mutation Taster		=72/28	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs766005493; hg19: chr1-11807541;