10-133127328-C-A

Variant names:

• chr10-133127328-C-A
• rs1852395994
• NM_001083909.3:c.497C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001083909.3(ADGRA1):​c.497C>A​(p.Ala166Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. A166V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADGRA1 NM_001083909.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.59
• Publications: 0 publications found

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]

ENSG00000297384 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001083909.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRA1	NM_001083909.3	MANE Select	c.497C>A	p.Ala166Glu	missense	Exon 6 of 7	NP_001077378.1	Q86SQ6-3
	ADGRA1	NM_001291085.2		c.206C>A	p.Ala69Glu	missense	Exon 3 of 4	NP_001278014.1	Q86SQ6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRA1	ENST00000392607.8	TSL:5 MANE Select	c.497C>A	p.Ala166Glu	missense	Exon 6 of 7	ENSP00000376384.3	Q86SQ6-3
	ADGRA1	ENST00000392606.2	TSL:1	c.206C>A	p.Ala69Glu	missense	Exon 3 of 4	ENSP00000376383.2	Q86SQ6-2
	ADGRA1	ENST00000864054.1		c.497C>A	p.Ala166Glu	missense	Exon 5 of 6	ENSP00000534113.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1439374 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 715538

African (AFR) AF: 0.00 AC: 0 AN: 32040

American (AMR) AF: 0.00 AC: 0 AN: 41656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25676

East Asian (EAS) AF: 0.00 AC: 0 AN: 37672

South Asian (SAS) AF: 0.00 AC: 0 AN: 82688

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1101850

Other (OTH) AF: 0.00 AC: 0 AN: 59522

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.085	D
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Uncertain	0.98
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.31
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.49	T
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-1.0	T
PhyloP100		5.6
PrimateAI	Uncertain	0.68	T
Sift4G	Benign	0.065	T
Polyphen		0.24	B
Vest4		0.61
MutPred		0.77		Gain of disorder (P = 0.0475)
MVP		0.043
ClinPred		0.97	D
GERP RS		3.6
Varity_R		0.30
Mutation Taster		=71/29	polymorphism

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

Other links and lift over

dbSNP: rs1852395994; hg19: chr10-134940832;