chr14-88011069-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_003608.4(GPR65):​c.222C>A​(p.Thr74Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP7: Synonymous conserved (PhyloP=-0.196 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR65	NM_003608.4	MANE Select	c.222C>A	p.Thr74Thr	synonymous	Exon 2 of 2	NP_003599.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR65	ENST00000267549.5	TSL:1 MANE Select	c.222C>A	p.Thr74Thr	synonymous	Exon 2 of 2	ENSP00000267549.3
	LINC01147	ENST00000554433.1	TSL:3	n.150+96G>T		intron	N/A
	LINC01147	ENST00000716957.1		n.500+96G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.54
DANN	Benign	0.46
PhyloP100		-0.20

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;