10-123666702-G-A

Variant names:

• chr10-123666702-G-A
• NM_153442.4:c.295G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_153442.4(GPR26):​c.295G>A​(p.Ala99Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: GPR26 NM_153442.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.81
• Publications: 0 publications found

Genes affected

GPR26 (HGNC:4481): (G protein-coupled receptor 26) This gene encodes a G protein-couple receptor protein. G-protein-coupled receptors are a large family of membrane proteins that are involved in cellular responses to environmental stimuli, neurotransmitters, and hormones. The encoded protein may play a role in neurodegenerative diseases. Epigenetic silencing of this gene has been observed in gliomas. [provided by RefSeq, Sep 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.9

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153442.4. 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
	GPR26	NM_153442.4	MANE Select	c.295G>A	p.Ala99Thr	missense	Exon 1 of 3	NP_703143.1	Q8NDV2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR26	ENST00000284674.2	TSL:1 MANE Select	c.295G>A	p.Ala99Thr	missense	Exon 1 of 3	ENSP00000284674.1	Q8NDV2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1446916 Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1 AN XY: 720060

African (AFR) AF: 0.00 AC: 0 AN: 33342

American (AMR) AF: 0.00 AC: 0 AN: 44438

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26024

East Asian (EAS) AF: 0.00 AC: 0 AN: 39478

South Asian (SAS) AF: 0.00 AC: 0 AN: 85606

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42098

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1110116

Other (OTH) AF: 0.00 AC: 0 AN: 60072

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Uncertain	0.059	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.14	T
Eigen	Pathogenic	0.72
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.011	T
MetaRNN	Pathogenic	0.90	D
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		9.8
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.34
Sift	Benign	0.11	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.87
MutPred		0.78		Loss of stability (P = 0.1375)
MVP		0.61
MPC		2.0
ClinPred		0.99	D
GERP RS		4.1
PromoterAI		-0.054	Neutral
Varity_R		0.33
gMVP		0.86
Mutation Taster		=66/34	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

hg19: chr10-125426218; COSMIC: COSV52936362;