X-79170974-C-T

Variant names:

• chrX-79170974-C-T
• rs3810712
• NM_032553.3:c.-34C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_032553.3(GPR174):​c.-34C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (10748 hom., 17057 hem., cov: 23)
  • Exomes 𝑓: 0.57 (116135 hom. 177721 hem.)
  • Failed GnomAD Quality Control
• Consequence: GPR174 NM_032553.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0140
• Publications: 10 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant X-79170974-C-T is Benign according to our data. Variant chrX-79170974-C-T is described in ClinVar as Benign. ClinVar VariationId is 1314975.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR174	NM_032553.3	c.-34C>T		5_prime_UTR_variant	Exon 3 of 3	ENST00000645147.2	NP_115942.1
GPR174	XM_047442579.1	c.-34C>T		5_prime_UTR_variant	Exon 3 of 3		XP_047298535.1
GPR174	XM_047442580.1	c.-34C>T		5_prime_UTR_variant	Exon 2 of 2		XP_047298536.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPR174	ENST00000645147.2	c.-34C>T		5_prime_UTR_variant	Exon 3 of 3		NM_032553.3	ENSP00000494310.1

Frequencies

GnomAD3 genomes AF: 0.515 AC: 57160 AN: 110944 Hom.: 10752 Cov.: 23

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.590

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.642

Gnomad MID AF: 0.523

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.518

GnomAD2 exomes AF: 0.501 AC: 67677 AN: 135092 AF XY: 0.516

Gnomad AFR exome AF: 0.409

Gnomad AMR exome AF: 0.272

Gnomad ASJ exome AF: 0.479

Gnomad EAS exome AF: 0.395

Gnomad FIN exome AF: 0.625

Gnomad NFE exome AF: 0.594

Gnomad OTH exome AF: 0.547

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.566 AC: 577287 AN: 1019570 Hom.: 116135 Cov.: 23 AF XY: 0.558 AC XY: 177721 AN XY: 318320

African (AFR) AF: 0.412 AC: 9897 AN: 24037

American (AMR) AF: 0.292 AC: 7765 AN: 26588

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 7515 AN: 15581

East Asian (EAS) AF: 0.470 AC: 13938 AN: 29634

South Asian (SAS) AF: 0.425 AC: 19097 AN: 44928

European-Finnish (FIN) AF: 0.628 AC: 23978 AN: 38188

Middle Eastern (MID) AF: 0.588 AC: 2247 AN: 3823

European-Non Finnish (NFE) AF: 0.591 AC: 469269 AN: 793825

Other (OTH) AF: 0.549 AC: 23581 AN: 42966

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.515 AC: 57173 AN: 110997 Hom.: 10748 Cov.: 23 AF XY: 0.513 AC XY: 17057 AN XY: 33261

African (AFR) AF: 0.415 AC: 12665 AN: 30536

American (AMR) AF: 0.420 AC: 4414 AN: 10505

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1243 AN: 2639

East Asian (EAS) AF: 0.403 AC: 1406 AN: 3493

South Asian (SAS) AF: 0.415 AC: 1101 AN: 2652

European-Finnish (FIN) AF: 0.642 AC: 3815 AN: 5943

Middle Eastern (MID) AF: 0.533 AC: 114 AN: 214

European-Non Finnish (NFE) AF: 0.591 AC: 31231 AN: 52828

Other (OTH) AF: 0.520 AC: 783 AN: 1507

Alfa AF: 0.551 Hom.: 37355

Bravo AF: 0.492

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Nov 01, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.6
DANN	Benign	0.70
PhyloP100		0.014
Mutation Taster		=300/0	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: rs3810712; hg19: chrX-78426471; COSMIC: COSV52132079;