chr3-71754093-C-T

Variant names:

• chr3-71754093-C-T
• rs1164655518
• NM_018971.3:c.44C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018971.3(GPR27):​c.44C>T​(p.Ala15Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000214 in 1,355,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: GPR27 NM_018971.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.82
• Publications: 2 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19559923).

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.44C>T	p.Ala15Val	missense	Exon 1 of 1	NP_061844.1	F1DAM3
	EIF4E3	NM_001134649.3		c.-291+122G>A		intron	N/A	NP_001128121.1	Q8N5X7-2
	EIF4E3	NM_173359.5		c.-291+551G>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.44C>T	p.Ala15Val	missense	Exon 1 of 1	ENSP00000303149.2	Q9NS67
	ENSG00000285708	ENST00000647725.1		c.-959+122G>A		intron	N/A	ENSP00000497585.1
	EIF4E3	ENST00000421769.6	TSL:1	c.-291+551G>A		intron	N/A	ENSP00000411762.2	Q8N5X7-2

Frequencies

GnomAD3 genomes AF: 0.00000673 AC: 1 AN: 148496 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000150

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000366 AC: 3 AN: 82034 AF XY: 0.0000206

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000825

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000232 AC: 28 AN: 1207254 Hom.: 0 Cov.: 32 AF XY: 0.0000184 AC XY: 11 AN XY: 597106

African (AFR) AF: 0.00 AC: 0 AN: 23446

American (AMR) AF: 0.00 AC: 0 AN: 20642

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18012

East Asian (EAS) AF: 0.00 AC: 0 AN: 23078

South Asian (SAS) AF: 0.00 AC: 0 AN: 66360

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28586

Middle Eastern (MID) AF: 0.000306 AC: 1 AN: 3264

European-Non Finnish (NFE) AF: 0.0000266 AC: 26 AN: 977624

Other (OTH) AF: 0.0000216 AC: 1 AN: 46242

GnomAD4 genome AF: 0.00000673 AC: 1 AN: 148496 Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 1 AN XY: 72332

African (AFR) AF: 0.00 AC: 0 AN: 41110

American (AMR) AF: 0.00 AC: 0 AN: 14958

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3396

East Asian (EAS) AF: 0.00 AC: 0 AN: 5140

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9268

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000150 AC: 1 AN: 66512

Other (OTH) AF: 0.00 AC: 0 AN: 2052

Alfa AF: 0.00 Hom.: 0

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	0.13
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.45	T
M_CAP	Pathogenic	0.45	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.8
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.064
Sift	Benign	0.34	T
Sift4G	Benign	0.33	T
Polyphen		0.72	P
Vest4		0.21
MutPred		0.39		Loss of disorder (P = 0.0452)
MVP		0.25
ClinPred		0.11	T
GERP RS		1.9
PromoterAI		-0.039	Neutral
Varity_R		0.071
gMVP		0.054
Mutation Taster		=87/13	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: rs1164655518; hg19: chr3-71803244;