Genetic Variant GALR3:p.Ala220Val (chr22-37825022-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003614.2(GALR3):c.659C>T(p.Ala220Val) variant causes a missense 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GALR3
NM_003614.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.760

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13552743).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003614.2. 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
	GALR3	NM_003614.2	MANE Select	c.659C>T	p.Ala220Val	missense	Exon 2 of 2	NP_003605.1	O60755

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALR3	ENST00000249041.3	TSL:1 MANE Select	c.659C>T	p.Ala220Val	missense	Exon 2 of 2	ENSP00000249041.2	O60755
	GALR3	ENST00000910168.1		c.659C>T	p.Ala220Val	missense	Exon 3 of 3	ENSP00000580227.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1010090

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

475906

African (AFR)

AF:

0.00

AC:

AN:

20064

American (AMR)

AF:

0.00

AC:

AN:

6160

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11052

East Asian (EAS)

AF:

0.00

AC:

AN:

19936

South Asian (SAS)

AF:

0.00

AC:

AN:

18876

European-Finnish (FIN)

AF:

0.00

AC:

AN:

18362

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2524

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

874742

Other (OTH)

AF:

0.00

AC:

AN:

38374

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.024

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.50

M_CAP

Benign

0.052

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

PhyloP100

0.76

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.34

REVEL

Benign

0.080

Sift

Benign

0.31

Sift4G

Benign

0.39

Polyphen

0.76

Vest4

0.14

MutPred

0.48

Gain of catalytic residue at A220 (P = 0.0288)

MVP

0.53

MPC

0.94

ClinPred

0.32

GERP RS

3.9

Varity_R

0.12

gMVP

0.18

Mutation Taster

=88/12

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over