14-88011069-C-T

Variant names:

• chr14-88011069-C-T
• rs6574978
• NM_003608.4:c.222C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003608.4(GPR65):​c.222C>T​(p.Thr74Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 1,612,534 control chromosomes in the GnomAD database, including 404,850 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.73 (40643 hom., cov: 33)
  • Exomes 𝑓: 0.70 (364207 hom.)
• Consequence: GPR65 NM_003608.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.196
• Publications: 29 publications found

Genes affected

GPR65 (HGNC:4517): (G protein-coupled receptor 65) Enables G protein-coupled receptor activity. Involved in several processes, including actin cytoskeleton reorganization; activation of GTPase activity; and positive regulation of stress fiber assembly. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

LINC01147 (HGNC:49468): (long intergenic non-protein coding RNA 1147)

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP7: Synonymous conserved (PhyloP=-0.196 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003608.4. 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
	GPR65	NM_003608.4	MANE Select	c.222C>T	p.Thr74Thr	synonymous	Exon 2 of 2	NP_003599.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR65	ENST00000267549.5	TSL:1 MANE Select	c.222C>T	p.Thr74Thr	synonymous	Exon 2 of 2	ENSP00000267549.3	Q8IYL9
	GPR65	ENST00000905165.1		c.222C>T	p.Thr74Thr	synonymous	Exon 2 of 2	ENSP00000575224.1
	LINC01147	ENST00000554433.1	TSL:3	n.150+96G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110522 AN: 151992 Hom.: 40609 Cov.: 33

Gnomad AFR AF: 0.769

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.801

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.981

Gnomad SAS AF: 0.854

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.701

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.711

GnomAD2 exomes AF: 0.749 AC: 188122 AN: 251156 AF XY: 0.746

Gnomad AFR exome AF: 0.769

Gnomad AMR exome AF: 0.869

Gnomad ASJ exome AF: 0.645

Gnomad EAS exome AF: 0.983

Gnomad FIN exome AF: 0.640

Gnomad NFE exome AF: 0.677

Gnomad OTH exome AF: 0.711

GnomAD4 exome AF: 0.702 AC: 1025498 AN: 1460424 Hom.: 364207 Cov.: 37 AF XY: 0.705 AC XY: 512574 AN XY: 726620

African (AFR) AF: 0.766 AC: 25617 AN: 33446

American (AMR) AF: 0.861 AC: 38506 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 16811 AN: 26124

East Asian (EAS) AF: 0.978 AC: 38839 AN: 39698

South Asian (SAS) AF: 0.849 AC: 73228 AN: 86234

European-Finnish (FIN) AF: 0.644 AC: 34407 AN: 53390

Middle Eastern (MID) AF: 0.712 AC: 4108 AN: 5768

European-Non Finnish (NFE) AF: 0.676 AC: 750662 AN: 1110708

Other (OTH) AF: 0.718 AC: 43320 AN: 60342

GnomAD4 genome AF: 0.727 AC: 110612 AN: 152110 Hom.: 40643 Cov.: 33 AF XY: 0.729 AC XY: 54191 AN XY: 74346

African (AFR) AF: 0.769 AC: 31897 AN: 41496

American (AMR) AF: 0.802 AC: 12246 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.642 AC: 2227 AN: 3468

East Asian (EAS) AF: 0.981 AC: 5083 AN: 5184

South Asian (SAS) AF: 0.854 AC: 4112 AN: 4816

European-Finnish (FIN) AF: 0.636 AC: 6721 AN: 10568

Middle Eastern (MID) AF: 0.688 AC: 201 AN: 292

European-Non Finnish (NFE) AF: 0.677 AC: 46005 AN: 67986

Other (OTH) AF: 0.713 AC: 1505 AN: 2112

Alfa AF: 0.706 Hom.: 41135

Bravo AF: 0.740

Asia WGS AF: 0.868 AC: 3018 AN: 3478

EpiCase AF: 0.691

EpiControl AF: 0.692

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.81
DANN	Benign	0.38
PhyloP100		-0.20
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: rs6574978; hg19: chr14-88477413; COSMIC: COSV108033625;