X-79171270-C-A

Variant names:

• chrX-79171270-C-A
• rs147721174
• NM_032553.3:c.263C>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_032553.3(GPR174):​c.263C>A​(p.Pro88His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00284 in 1,209,893 control chromosomes in the GnomAD database, including 8 homozygotes. There are 1,133 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0019 (2 hom., 52 hem., cov: 23)
  • Exomes 𝑓: 0.0029 (6 hom. 1081 hem.)
• Consequence: GPR174 NM_032553.3 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.12
• Publications: 4 publications found

Genes affected

GPR174 (HGNC:30245): (G protein-coupled receptor 174) This gene encodes a protein belonging to the G protein-coupled receptor superfamily. These proteins are characterized by the presence of seven alpha-helical transmembrane domains, and they activate or interact with various endogenous or exogenous ligands, including neurotransmitters, hormones, and odorant and taste substances. This family member is classified as an orphan receptor because the cognate ligand has not been identified. [provided by RefSeq, Sep 2011]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007401705).
• BP6: Variant X-79171270-C-A is Benign according to our data. Variant chrX-79171270-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3041228.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032553.3. 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
	GPR174	NM_032553.3	MANE Select	c.263C>A	p.Pro88His	missense	Exon 3 of 3	NP_115942.1	Q9BXC1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR174	ENST00000645147.2	MANE Select	c.263C>A	p.Pro88His	missense	Exon 3 of 3	ENSP00000494310.1	Q9BXC1
	GPR174	ENST00000871945.1		c.263C>A	p.Pro88His	missense	Exon 2 of 2	ENSP00000542004.1

Frequencies

GnomAD3 genomes AF: 0.00185 AC: 208 AN: 112172 Hom.: 2 Cov.: 23

Gnomad AFR AF: 0.000453

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00160

Gnomad ASJ AF: 0.000377

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00298

Gnomad FIN AF: 0.000328

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00308

Gnomad OTH AF: 0.00133

GnomAD2 exomes AF: 0.00220 AC: 401 AN: 181889 AF XY: 0.00241

Gnomad AFR exome AF: 0.000685

Gnomad AMR exome AF: 0.00183

Gnomad ASJ exome AF: 0.000538

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000315

Gnomad NFE exome AF: 0.00294

Gnomad OTH exome AF: 0.00357

GnomAD4 exome AF: 0.00294 AC: 3231 AN: 1097666 Hom.: 6 Cov.: 33 AF XY: 0.00298 AC XY: 1081 AN XY: 363100

African (AFR) AF: 0.000455 AC: 12 AN: 26394

American (AMR) AF: 0.00179 AC: 63 AN: 35177

Ashkenazi Jewish (ASJ) AF: 0.000413 AC: 8 AN: 19373

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30166

South Asian (SAS) AF: 0.00431 AC: 233 AN: 54094

European-Finnish (FIN) AF: 0.000543 AC: 22 AN: 40481

Middle Eastern (MID) AF: 0.00653 AC: 27 AN: 4133

European-Non Finnish (NFE) AF: 0.00325 AC: 2735 AN: 841774

Other (OTH) AF: 0.00282 AC: 130 AN: 46074

GnomAD4 genome AF: 0.00185 AC: 208 AN: 112227 Hom.: 2 Cov.: 23 AF XY: 0.00151 AC XY: 52 AN XY: 34423

African (AFR) AF: 0.000452 AC: 14 AN: 30951

American (AMR) AF: 0.00160 AC: 17 AN: 10635

Ashkenazi Jewish (ASJ) AF: 0.000377 AC: 1 AN: 2653

East Asian (EAS) AF: 0.00 AC: 0 AN: 3570

South Asian (SAS) AF: 0.00299 AC: 8 AN: 2678

European-Finnish (FIN) AF: 0.000328 AC: 2 AN: 6106

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.00308 AC: 164 AN: 53206

Other (OTH) AF: 0.00131 AC: 2 AN: 1527

Alfa AF: 0.00260 Hom.: 109

Bravo AF: 0.00218

TwinsUK AF: 0.00324 AC: 12

ALSPAC AF: 0.00312 AC: 9

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00223 AC: 15

ExAC AF: 0.00231 AC: 281

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	GPR174-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	10
DANN	Benign	0.87
DEOGEN2	Benign	0.0052	T
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.0074	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.29	N
PhyloP100		1.1
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.33	N
REVEL	Benign	0.082
Sift	Benign	0.14	T
Sift4G	Benign	0.14	T
Polyphen		0.0	B
Vest4		0.057
MVP		0.16
MPC		0.29
ClinPred		0.0022	T
GERP RS		3.0
Varity_R		0.20
gMVP		0.67
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs147721174; hg19: chrX-78426767;