chr3-71754069-C-T

Variant names:

• chr3-71754069-C-T
• rs767696710
• NM_018971.3:c.20C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_018971.3(GPR27):​c.20C>T​(p.Pro7Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000121 in 1,152,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: GPR27 NM_018971.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.625
• Publications: 0 publications found

Genes affected

GPR27 (HGNC:4482): (G protein-coupled receptor 27) GPR27 is a member of the G protein-coupled receptors (GPCRs), a large family of receptors that have a similar structure characterized by 7 transmembrane domains. Activation of GPCRs by extracellular stimuli such as neurotransmitters, hormones, or light induces an intracellular signaling cascade mediated by heterotrimeric GTP-binding proteins, or G proteins.[supplied by OMIM, May 2010]

ENSG00000285708 (HGNC:):

EIF4E3 (HGNC:31837): (eukaryotic translation initiation factor 4E family member 3) EIF4E3 belongs to the EIF4E family of translational initiation factors that interact with the 5-prime cap structure of mRNA and recruit mRNA to the ribosome (Joshi et al., 2004 [PubMed 15153109]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004034966).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018971.3. 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
	GPR27	NM_018971.3	MANE Select	c.20C>T	p.Pro7Leu	missense	Exon 1 of 1	NP_061844.1	F1DAM3
	EIF4E3	NM_001134649.3		c.-291+146G>A		intron	N/A	NP_001128121.1	Q8N5X7-2
	EIF4E3	NM_173359.5		c.-291+575G>A		intron	N/A	NP_775495.1	Q8N5X7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR27	ENST00000304411.3	TSL:6 MANE Select	c.20C>T	p.Pro7Leu	missense	Exon 1 of 1	ENSP00000303149.2	Q9NS67
	ENSG00000285708	ENST00000647725.1		c.-959+146G>A		intron	N/A	ENSP00000497585.1
	EIF4E3	ENST00000421769.6	TSL:1	c.-291+575G>A		intron	N/A	ENSP00000411762.2	Q8N5X7-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000196 AC: 1 AN: 50954 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000648

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000121 AC: 14 AN: 1152960 Hom.: 0 Cov.: 32 AF XY: 0.00000882 AC XY: 5 AN XY: 567114

African (AFR) AF: 0.00 AC: 0 AN: 22294

American (AMR) AF: 0.00 AC: 0 AN: 15896

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15584

East Asian (EAS) AF: 0.000423 AC: 9 AN: 21252

South Asian (SAS) AF: 0.0000339 AC: 2 AN: 58924

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26004

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3004

European-Non Finnish (NFE) AF: 0.00000317 AC: 3 AN: 946498

Other (OTH) AF: 0.00 AC: 0 AN: 43504

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000110 AC: 1

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	Benign	0.14
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.58	T
MetaRNN	Benign	0.0040	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.63
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.41	N
REVEL	Benign	0.056
Sift	Benign	0.24	T
Sift4G	Benign	0.24	T
Polyphen		0.0	B
Vest4		0.056
MutPred		0.21		Loss of relative solvent accessibility (P = 0.008)
MVP		0.043
ClinPred		0.035	T
GERP RS		0.87
PromoterAI		0.030	Neutral
Varity_R		0.063
gMVP		0.060
Mutation Taster		=94/6	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: rs767696710; hg19: chr3-71803220;