10-123666606-G-T

Variant summary

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

The NM_153442.4(GPR26):c.199G>T(p.Val67Phe) 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: 34)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GPR26 NM_153442.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.40

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

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=0.3321275).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR26	NM_153442.4	c.199G>T	p.Val67Phe	missense_variant	1/3	ENST00000284674.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR26	ENST00000284674.2	c.199G>T	p.Val67Phe	missense_variant	1/3	1	NM_153442.4	P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.95e-7 AC: 1 AN: 1439748 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 715126

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: 0.0000119

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 29, 2021

The c.199G>T (p.V67F) alteration is located in exon 1 (coding exon 1) of the GPR26 gene. This alteration results from a G to T substitution at nucleotide position 199, causing the valine (V) at amino acid position 67 to be replaced by a phenylalanine (F). 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	0.33
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
Cadd	Uncertain	25
Dann	Uncertain	0.99
DEOGEN2	Benign	0.044	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Benign	0.53	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.18
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.023	D
Polyphen		0.99	D
Vest4		0.18
MutPred		0.68		Loss of helix (P = 0.1706);
MVP		0.26
MPC		2.3
ClinPred		0.85	D
GERP RS		3.1
Varity_R		0.34
gMVP		0.75

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: rs1328536063; hg19: chr10-125426122;