1-11748471-C-G

Variant names:

• chr1-11748471-C-G
• NM_020350.5:c.225C>G

Variant summary

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

The NM_020350.5(AGTRAP):​c.225C>G​(p.Phe75Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: AGTRAP NM_020350.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.38

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGTRAP	NM_020350.5	c.225C>G	p.Phe75Leu	missense_variant	Exon 4 of 5	ENST00000314340.10	NP_065083.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGTRAP	ENST00000314340.10	c.225C>G	p.Phe75Leu	missense_variant	Exon 4 of 5	1	NM_020350.5	ENSP00000319713.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 14, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.225C>G (p.F75L) alteration is located in exon 4 (coding exon 4) of the AGTRAP gene. This alteration results from a C to G substitution at nucleotide position 225, causing the phenylalanine (F) at amino acid position 75 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Benign	0.62
DEOGEN2	Benign	0.19	.;T
Eigen	Benign	0.013
Eigen_PC	Benign	-0.013
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.57	D;D
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.7	M;M
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-3.7	D;D
REVEL	Benign	0.24
Sift	Benign	0.073	T;D
Sift4G	Uncertain	0.059	T;T
Polyphen		0.68	P;P
Vest4		0.46
MutPred		0.77		Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP		0.56
MPC		0.64
ClinPred		0.94	D
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
gMVP		0.82

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: chr1-11808528;