22-37825037-C-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_003614.2(GALR3):​c.674C>A​(p.Ala225Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00101 in 1,152,814 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00056 ( 1 hom., cov: 34)
Exomes 𝑓: 0.0011 ( 2 hom. )

Consequence

GALR3
NM_003614.2 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.32
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.26306155).
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GALR3NM_003614.2 linkc.674C>A p.Ala225Glu 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
GALR3ENST00000249041.3 linkc.674C>A p.Ala225Glu missense_variant Exon 2 of 2 1 NM_003614.2 ENSP00000249041.2 O60755

Frequencies

GnomAD3 genomes
AF:
0.000561
AC:
83
AN:
148058
Hom.:
1
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.000341
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000336
Gnomad ASJ
AF:
0.000588
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000933
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00107
AC:
1077
AN:
1004756
Hom.:
2
Cov.:
32
AF XY:
0.00108
AC XY:
510
AN XY:
473504
show subpopulations
Gnomad4 AFR exome
AF:
0.000201
Gnomad4 AMR exome
AF:
0.000167
Gnomad4 ASJ exome
AF:
0.000559
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00118
Gnomad4 OTH exome
AF:
0.000975
GnomAD4 genome
AF:
0.000561
AC:
83
AN:
148058
Hom.:
1
Cov.:
34
AF XY:
0.000486
AC XY:
35
AN XY:
72064
show subpopulations
Gnomad4 AFR
AF:
0.000341
Gnomad4 AMR
AF:
0.000336
Gnomad4 ASJ
AF:
0.000588
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000933
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000902
Hom.:
0
Bravo
AF:
0.000657
ExAC
AF:
0.000160
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 01, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.674C>A (p.A225E) alteration is located in exon 2 (coding exon 2) of the GALR3 gene. This alteration results from a C to A substitution at nucleotide position 674, causing the alanine (A) at amino acid position 225 to be replaced by a glutamic acid (E). 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
0.10
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.36
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.031
T
Eigen
Benign
-0.020
Eigen_PC
Benign
-0.0061
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.35
T
M_CAP
Uncertain
0.29
D
MetaRNN
Benign
0.26
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.97
N
PrimateAI
Pathogenic
0.94
D
PROVEAN
Benign
0.31
N
REVEL
Benign
0.28
Sift
Benign
0.055
T
Sift4G
Benign
0.13
T
Polyphen
1.0
D
Vest4
0.43
MVP
0.59
MPC
2.1
ClinPred
0.98
D
GERP RS
3.6
Varity_R
0.27
gMVP
0.27

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.

Other links and lift over

dbSNP: rs749411626; hg19: chr22-38221044; API