Variant chr10-133102798-C-G 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.357C>G(p.Cys119Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000363 in 1,460,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

ADGRA1
NM_001083909.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0300

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=0.24278069).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ADGRA1	NM_001083909.3 linkuse as main transcript	c.357C>G	p.Cys119Trp	missense_variant	5/7	ENST00000392607.8
ADGRA1	NM_001291085.2 linkuse as main transcript	c.66C>G	p.Cys22Trp	missense_variant	2/4
ADGRA1	XM_017016779.2 linkuse as main transcript	c.357C>G	p.Cys119Trp	missense_variant	4/5
ADGRA1	XM_011540273.1 linkuse as main transcript	c.-107+4035C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRA1	ENST00000392607.8 linkuse as main transcript	c.357C>G	p.Cys119Trp	missense_variant	5/7	5	NM_001083909.3	P1	Q86SQ6-3
ADGRA1	ENST00000392606.2 linkuse as main transcript	c.66C>G	p.Cys22Trp	missense_variant	2/4	1			Q86SQ6-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

249672

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135496

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000363

AC:

AN:

1460466

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

726562

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

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:

0.0000441

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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

Oct 12, 2022

The c.357C>G (p.C119W) alteration is located in exon 5 (coding exon 4) of the ADGRA1 gene. This alteration results from a C to G substitution at nucleotide position 357, causing the cysteine (C) at amino acid position 119 to be replaced by a tryptophan (W). 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

0.20

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.14

.;T;.

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.49

T;T;T

M_CAP

Benign

0.032

MetaRNN

Benign

0.24

T;T;T

MetaSVM

Benign

-0.87

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-4.7

.;D;D

REVEL

Benign

0.11

Sift

Benign

0.17

.;T;T

Sift4G

Pathogenic

0.0010

D;D;D

Polyphen

0.97

D;D;.

Vest4

0.43

MutPred

0.37

.;Loss of catalytic residue at L120 (P = 0.0076);.;

MVP

0.068

MPC

1.4

ClinPred

0.84

GERP RS

2.1

Varity_R

0.16

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over