22-37824851-C-G

Variant names:

• chr22-37824851-C-G
• rs765841018
• NM_003614.2:c.488C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003614.2(GALR3):​c.488C>G​(p.Thr163Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000789 in 1,267,110 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. 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. T163I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: GALR3 NM_003614.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.28
• Publications: 0 publications found

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]

ACMG classification

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=0.32588318).

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.488C>G	p.Thr163Ser	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.488C>G	p.Thr163Ser	missense	Exon 2 of 2	ENSP00000249041.2	O60755
	GALR3	ENST00000910168.1		c.488C>G	p.Thr163Ser	missense	Exon 3 of 3	ENSP00000580227.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.89e-7 AC: 1 AN: 1267110 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 627036

African (AFR) AF: 0.00 AC: 0 AN: 26812

American (AMR) AF: 0.00 AC: 0 AN: 28802

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20914

East Asian (EAS) AF: 0.00 AC: 0 AN: 29374

South Asian (SAS) AF: 0.00 AC: 0 AN: 62906

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31260

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4044

European-Non Finnish (NFE) AF: 9.87e-7 AC: 1 AN: 1012714

Other (OTH) AF: 0.00 AC: 0 AN: 50284

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	23
DANN	Benign	0.89
DEOGEN2	Benign	0.030	T
Eigen	Benign	0.11
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.58	T
M_CAP	Pathogenic	0.45	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		3.3
PrimateAI	Pathogenic	0.95	D
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.087
Sift	Benign	0.53	T
Sift4G	Benign	0.82	T
Polyphen		0.67	P
Vest4		0.15
MutPred		0.60		Loss of phosphorylation at T163 (P = 0.1984)
MVP		0.49
MPC		1.3
ClinPred		0.43	T
GERP RS		4.8
Varity_R		0.20
gMVP		0.23
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs765841018; hg19: chr22-38220858;