10-133128441-C-T

Variant names:

• chr10-133128441-C-T
• rs1852426049
• NM_001083909.3:c.613C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001083909.3(ADGRA1):​c.613C>T​(p.Pro205Ser) variant causes a missense change. 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: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADGRA1 NM_001083909.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.64

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28907222).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRA1	NM_001083909.3	c.613C>T	p.Pro205Ser	missense_variant	Exon 7 of 7	ENST00000392607.8	NP_001077378.1
ADGRA1	NM_001291085.2	c.322C>T	p.Pro108Ser	missense_variant	Exon 4 of 4		NP_001278014.1
ADGRA1	XM_011540273.1	c.106C>T	p.Pro36Ser	missense_variant	Exon 3 of 3		XP_011538575.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRA1	ENST00000392607.8	c.613C>T	p.Pro205Ser	missense_variant	Exon 7 of 7	5	NM_001083909.3	ENSP00000376384.3
ADGRA1	ENST00000392606.2	c.322C>T	p.Pro108Ser	missense_variant	Exon 4 of 4	1		ENSP00000376383.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1451180 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 721372

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.: 30

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 22, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.613C>T (p.P205S) alteration is located in exon 7 (coding exon 6) of the ADGRA1 gene. This alteration results from a C to T substitution at nucleotide position 613, causing the proline (P) at amino acid position 205 to be replaced by a serine (S). 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	0.17
BayesDel_addAF	Uncertain	0.044	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.15	.;T;.
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Benign	-0.84	T
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-5.2	.;D;.
REVEL	Benign	0.17
Sift	Benign	0.058	.;T;.
Sift4G	Uncertain	0.0050	D;D;D
Polyphen		0.72	P;P;.
Vest4		0.24
MutPred		0.62		.;Gain of phosphorylation at P205 (P = 0.0101);.;
MVP		0.37
MPC		1.3
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.38
gMVP		0.58

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

LitVar

Other links and lift over

dbSNP: rs1852426049; hg19: chr10-134941945;