dbSNP rs771463474: GALR3:p.Ala300Thr (chr22-37825261-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_003614.2(GALR3):c.898G>A(p.Ala300Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000993 in 1,409,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A300S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

GALR3
NM_003614.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.33

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32645476).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALR3	NM_003614.2 link	c.898G>A	p.Ala300Thr	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.898G>A	p.Ala300Thr	missense_variant	Exon 2 of 2	1	NM_003614.2	ENSP00000249041.2		O60755

Frequencies

GnomAD3 genomes

AF:

0.00000669

AC:

AN:

149500

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:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000141

AC:

AN:

141956

AF XY:

0.0000121

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000947

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1260246

Hom.:

Cov.:

AF XY:

0.00000959

AC XY:

AN XY:

625340

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26508

American (AMR)

AF:

0.0000654

AC:

AN:

30592

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20112

East Asian (EAS)

AF:

0.00

AC:

AN:

27332

South Asian (SAS)

AF:

0.00

AC:

AN:

63678

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31654

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4890

European-Non Finnish (NFE)

AF:

0.00000894

AC:

AN:

1006240

Other (OTH)

AF:

0.0000406

AC:

AN:

49240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

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:

0.00000669

AC:

AN:

149500

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72888

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41154

American (AMR)

AF:

0.00

AC:

AN:

15056

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3416

East Asian (EAS)

AF:

0.00

AC:

AN:

5146

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9648

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000149

AC:

AN:

66964

Other (OTH)

AF:

0.00

AC:

AN:

2058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.025

Eigen

Benign

0.069

Eigen_PC

Benign

0.066

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.86

M_CAP

Pathogenic

0.59

MetaRNN

Benign

0.33

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

4.3

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.43

REVEL

Benign

0.13

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.041

Polyphen

0.99

Vest4

0.17

MutPred

0.29

Gain of catalytic residue at A300 (P = 0.0212);

MVP

0.44

MPC

1.1

ClinPred

0.78

GERP RS

1.9

Varity_R

0.17

gMVP

0.061

Mutation Taster

=75/25

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over