Genetic Variant GALR3:p.Thr163Ile (chr22-37824851-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003614.2(GALR3):c.488C>T(p.Thr163Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000316 in 1,267,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000032 ( 0 hom. )

Consequence

GALR3
NM_003614.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.28

Variant links:

Genes affected

GALR3 (HGNC:4134): (galanin receptor 3) The neuropeptide galanin modulates a variety of physiologic processes including cognition/memory, sensory/pain processing, hormone secretion, and feeding behavior. The human galanin receptors are G protein-coupled receptors that functionally couple to their intracellular effector through distinct signaling pathways. GALR3 is found in many tissues and may be expressed as 1.4-, 2.4-, and 5-kb transcripts [provided by RefSeq, Jul 2008]

GALR3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17021099).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALR3	NM_003614.2 link	c.488C>T	p.Thr163Ile	missense_variant	Exon 2 of 2	ENST00000249041.3	NP_003605.1	O60755

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALR3	ENST00000249041.3 link	c.488C>T	p.Thr163Ile	missense_variant	Exon 2 of 2	1	NM_003614.2	ENSP00000249041.2		O60755

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000157

AC:

AN:

127022

Hom.:

AF XY:

0.0000270

AC XY:

AN XY:

73996

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000166

Gnomad OTH exome

AF:

0.000344

GnomAD4 exome

AF:

0.00000316

AC:

AN:

1267110

Hom.:

Cov.:

AF XY:

0.00000159

AC XY:

AN XY:

627036

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000296

Gnomad4 OTH exome

AF:

0.0000199

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000886

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 21, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.488C>T (p.T163I) alteration is located in exon 2 (coding exon 2) of the GALR3 gene. This alteration results from a C to T substitution at nucleotide position 488, causing the threonine (T) at amino acid position 163 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.017

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.10

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.61

M_CAP

Pathogenic

0.42

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.56

PrimateAI

Pathogenic

0.96

PROVEAN

Benign

0.19

REVEL

Benign

0.096

Sift

Benign

0.63

Sift4G

Benign

0.41

Polyphen

0.027

Vest4

0.046

MutPred

0.50

Loss of phosphorylation at T163 (P = 0.0758);

MVP

0.39

MPC

0.99

ClinPred

0.25

GERP RS

4.8

Varity_R

0.16

gMVP

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over