Variant chr18-77250584-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM2BP4_Strong

The NM_001480.4(GALR1):c.36C>G(p.Asn12Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000174 in 1,543,906 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.00015 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00018 ( 1 hom. )

Consequence

GALR1
NM_001480.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.326

Variant links:

Genes affected

GALR1 (HGNC:4132): (galanin receptor 1) The neuropeptide galanin elicits a range of biological effects by interaction with specific G-protein-coupled receptors. Galanin receptors are seven-transmembrane proteins shown to activate a variety of intracellular second-messenger pathways. GALR1 inhibits adenylyl cyclase via a G protein of the Gi/Go family. GALR1 is widely expressed in the brain and spinal cord, as well as in peripheral sites such as the small intestine and heart. [provided by RefSeq, Jul 2008]

GALR1 links:

LOC124904329 (HGNC:):

LOC124904329 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM1

In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity GALR1_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03688571).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GALR1	NM_001480.4 linkuse as main transcript	c.36C>G	p.Asn12Lys	missense_variant	1/3	ENST00000299727.5
LOC124904329	XR_007066422.1 linkuse as main transcript	n.604+264G>C		intron_variant, non_coding_transcript_variant
GALR1	XM_017025691.2 linkuse as main transcript	c.36C>G	p.Asn12Lys	missense_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALR1	ENST00000299727.5 linkuse as main transcript	c.36C>G	p.Asn12Lys	missense_variant	1/3	1	NM_001480.4	P1

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000214

AC:

AN:

145058

Hom.:

AF XY:

0.000240

AC XY:

AN XY:

79208

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000199

Gnomad ASJ exome

AF:

0.000241

Gnomad EAS exome

AF:

0.0000898

Gnomad SAS exome

AF:

0.0000855

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000346

Gnomad OTH exome

AF:

0.000234

GnomAD4 exome

AF:

0.000176

AC:

245

AN:

1391720

Hom.:

Cov.:

AF XY:

0.000199

AC XY:

137

AN XY:

687552

show subpopulations

Gnomad4 AFR exome

AF:

0.000126

Gnomad4 AMR exome

AF:

0.000193

Gnomad4 ASJ exome

AF:

0.000278

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000625

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000168

Gnomad4 OTH exome

AF:

0.000414

GnomAD4 genome

AF:

0.000151

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.000217

Hom.:

Bravo

AF:

0.000140

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000126

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 05, 2023

The c.36C>G (p.N12K) alteration is located in exon 1 (coding exon 1) of the GALR1 gene. This alteration results from a C to G substitution at nucleotide position 36, causing the asparagine (N) at amino acid position 12 to be replaced by a lysine (K). 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

Uncertain

0.48

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.14

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.51

M_CAP

Benign

0.033

MetaRNN

Benign

0.037

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.3

REVEL

Benign

0.058

Sift

Benign

0.076

Sift4G

Benign

0.45

Polyphen

0.59

Vest4

0.58

MutPred

0.34

Gain of ubiquitination at N12 (P = 0.0025);

MVP

0.81

MPC

1.4

ClinPred

0.041

GERP RS

1.6

Varity_R

0.088

gMVP

0.56

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