Variant 10-133128876-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001083909.3(ADGRA1):c.1048G>T(p.Gly350Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ADGRA1
NM_001083909.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.44

Variant links:

Genes affected

ADGRA1 (HGNC:13838): (adhesion G protein-coupled receptor A1) This gene encodes a protein that belongs to the adhesion family of G-protein-coupled receptors. Members of this family function in several sensory systems and regulate blood pressure, immune responses, food intake and development. A similar protein in rodents is thought to play a role in in the regulation of neuronal signaling pathways. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Mar 2014]

ADGRA1 links:

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ACMG classification

Classification made for transcript

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=0.19303426).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ADGRA1	NM_001083909.3 linkuse as main transcript	c.1048G>T	p.Gly350Cys	missense_variant	7/7	ENST00000392607.8
ADGRA1	NM_001291085.2 linkuse as main transcript	c.757G>T	p.Gly253Cys	missense_variant	4/4
ADGRA1	XM_011540273.1 linkuse as main transcript	c.541G>T	p.Gly181Cys	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRA1	ENST00000392607.8 linkuse as main transcript	c.1048G>T	p.Gly350Cys	missense_variant	7/7	5	NM_001083909.3	P1	Q86SQ6-3
ADGRA1	ENST00000392606.2 linkuse as main transcript	c.757G>T	p.Gly253Cys	missense_variant	4/4	1			Q86SQ6-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1418134

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

702580

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 02, 2024

The c.1048G>T (p.G350C) alteration is located in exon 7 (coding exon 6) of the ADGRA1 gene. This alteration results from a G to T substitution at nucleotide position 1048, causing the glycine (G) at amino acid position 350 to be replaced by a cysteine (C). 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

Benign

0.11

BayesDel_addAF

Benign

-0.092

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

.;T;.

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.55

T;T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-3.8

.;D;.

REVEL

Benign

0.073

Sift

Benign

0.040

.;D;.

Sift4G

Pathogenic

0.0010

D;D;D

Polyphen

0.86

P;D;.

Vest4

0.20

MutPred

0.23

.;Gain of catalytic residue at G350 (P = 0.0193);.;

MVP

0.20

MPC

1.2

ClinPred

0.83

GERP RS

0.32

Varity_R

0.21

gMVP

0.43

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over