rs200088833

Variant names:

• chr1-11747519-C-A
• NM_020350.5:c.142C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-11747519-C-A
• chr1-11747519-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001040196.2(AGTRAP):​c.239C>A​(p.Ala80Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict 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. A80V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: AGTRAP NM_001040196.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.651

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22068536).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGTRAP	NM_020350.5	c.142C>A	p.Arg48Arg	synonymous_variant	Exon 3 of 5	ENST00000314340.10	NP_065083.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGTRAP	ENST00000314340.10	c.142C>A	p.Arg48Arg	synonymous_variant	Exon 3 of 5	1	NM_020350.5	ENSP00000319713.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461756 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727174

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	8.0
DANN	Uncertain	0.98
DEOGEN2	Benign	0.057	.;.;T;.
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.51	T;T;T;T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.22	T;T;T;T
MetaSVM	Benign	-1.0	T
PROVEAN	Uncertain	-2.5	D;D;D;D
REVEL	Benign	0.099
Sift	Pathogenic	0.0	.;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		0.022	B;B;.;B
Vest4		0.49
MutPred		0.31		.;Gain of solvent accessibility (P = 9e-04);.;Gain of solvent accessibility (P = 9e-04);
MVP		0.56
ClinPred		0.49	T
GERP RS		0.73
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-11807576;