NM_004224.3:c.555C>T

Variant names:

• chrX-151180138-C-T
• rs182926090
• NM_004224.3:c.555C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_004224.3(GPR50):​c.555C>T​(p.Asn185Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00581 in 1,206,370 control chromosomes in the GnomAD database, including 20 homozygotes. There are 2,455 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0040 (0 hom., 129 hem., cov: 22)
  • Exomes 𝑓: 0.0060 (20 hom. 2326 hem.)
• Consequence: GPR50 NM_004224.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.02
• Publications: 1 publications found

Genes affected

GPR50 (HGNC:4506): (G protein-coupled receptor 50) This gene product belongs to the G-protein coupled receptor 1 family. Even though this protein shares similarity with the melatonin receptors, it does not bind melatonin, however, it inhibits melatonin receptor 1A function through heterodimerization. Polymorphic variants of this gene have been associated with bipolar affective disorder in women. [provided by RefSeq, Jan 2010]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant X-151180138-C-T is Benign according to our data. Variant chrX-151180138-C-T is described in ClinVar as Benign. ClinVar VariationId is 789366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.02 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.006 (6565/1094741) while in subpopulation SAS AF = 0.0163 (883/54132). AF 95% confidence interval is 0.0154. There are 20 homozygotes in GnomAdExome4. There are 2326 alleles in the male GnomAdExome4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 129 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004224.3. 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
	GPR50	NM_004224.3	MANE Select	c.555C>T	p.Asn185Asn	synonymous	Exon 2 of 2	NP_004215.2	Q13585

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR50	ENST00000218316.4	TSL:1 MANE Select	c.555C>T	p.Asn185Asn	synonymous	Exon 2 of 2	ENSP00000218316.3	Q13585

Frequencies

GnomAD3 genomes AF: 0.00398 AC: 444 AN: 111575 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.000587

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00303

Gnomad ASJ AF: 0.0148

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0130

Gnomad FIN AF: 0.000998

Gnomad MID AF: 0.0210

Gnomad NFE AF: 0.00571

Gnomad OTH AF: 0.00468

GnomAD2 exomes AF: 0.00561 AC: 1005 AN: 179054 AF XY: 0.00657

Gnomad AFR exome AF: 0.00104

Gnomad AMR exome AF: 0.00219

Gnomad ASJ exome AF: 0.0119

Gnomad EAS exome AF: 0.0000738

Gnomad FIN exome AF: 0.00106

Gnomad NFE exome AF: 0.00615

Gnomad OTH exome AF: 0.00743

GnomAD4 exome AF: 0.00600 AC: 6565 AN: 1094741 Hom.: 20 Cov.: 33 AF XY: 0.00644 AC XY: 2326 AN XY: 361177

African (AFR) AF: 0.000834 AC: 22 AN: 26387

American (AMR) AF: 0.00241 AC: 85 AN: 35206

Ashkenazi Jewish (ASJ) AF: 0.0127 AC: 247 AN: 19375

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30204

South Asian (SAS) AF: 0.0163 AC: 883 AN: 54132

European-Finnish (FIN) AF: 0.00116 AC: 44 AN: 37857

Middle Eastern (MID) AF: 0.00992 AC: 41 AN: 4135

European-Non Finnish (NFE) AF: 0.00594 AC: 5002 AN: 841402

Other (OTH) AF: 0.00521 AC: 240 AN: 46043

GnomAD4 genome AF: 0.00397 AC: 443 AN: 111629 Hom.: 0 Cov.: 22 AF XY: 0.00382 AC XY: 129 AN XY: 33793

African (AFR) AF: 0.000586 AC: 18 AN: 30708

American (AMR) AF: 0.00303 AC: 32 AN: 10575

Ashkenazi Jewish (ASJ) AF: 0.0148 AC: 39 AN: 2642

East Asian (EAS) AF: 0.00 AC: 0 AN: 3568

South Asian (SAS) AF: 0.0126 AC: 33 AN: 2612

European-Finnish (FIN) AF: 0.000998 AC: 6 AN: 6011

Middle Eastern (MID) AF: 0.0230 AC: 5 AN: 217

European-Non Finnish (NFE) AF: 0.00571 AC: 303 AN: 53099

Other (OTH) AF: 0.00462 AC: 7 AN: 1516

Alfa AF: 0.00633 Hom.: 45

Bravo AF: 0.00416

EpiCase AF: 0.00763

EpiControl AF: 0.00782

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	3.7
DANN	Benign	0.81
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs182926090; hg19: chrX-150348610;