dbSNP rs768648543: GALR3:p.Ala179Gly (chr22-37824899-C-G) – 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.536C>G(p.Ala179Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000264 in 1,364,358 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

GALR3
NM_003614.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.46

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=0.12958789).

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.536C>G	p.Ala179Gly	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.536C>G	p.Ala179Gly	missense	Exon 2 of 2	ENSP00000249041.2	O60755
	GALR3	ENST00000910168.1		c.536C>G	p.Ala179Gly	missense	Exon 3 of 3	ENSP00000580227.1

Frequencies

GnomAD3 genomes

AF:

0.0000133

AC:

AN:

150276

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000297

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000280

AC:

AN:

1214082

Hom.:

Cov.:

AF XY:

0.0000251

AC XY:

AN XY:

596930

show subpopulations

African (AFR)

AF:

0.0000392

AC:

AN:

25538

American (AMR)

AF:

0.00

AC:

AN:

21906

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18518

East Asian (EAS)

AF:

0.00

AC:

AN:

28782

South Asian (SAS)

AF:

0.00

AC:

AN:

51648

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28476

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3880

European-Non Finnish (NFE)

AF:

0.0000324

AC:

AN:

987326

Other (OTH)

AF:

0.0000208

AC:

AN:

48008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000133

AC:

AN:

150276

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73338

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41258

American (AMR)

AF:

0.00

AC:

AN:

15126

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3436

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9840

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000297

AC:

AN:

67322

Other (OTH)

AF:

0.00

AC:

AN:

2064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.00000902

AC:

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

0.064

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.026

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.058

M_CAP

Pathogenic

0.50

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

PhyloP100

1.5

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.35

REVEL

Benign

0.035

Sift

Benign

0.44

Sift4G

Benign

0.40

Polyphen

0.40

Vest4

0.080

MutPred

0.45

Gain of disorder (P = 0.3429)

MVP

0.31

MPC

1.4

ClinPred

0.17

GERP RS

-0.31

Varity_R

0.071

gMVP

0.17

Mutation Taster

=84/16

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over