rs947696712

Variant names:

• chr22-37824758-C-A
• NM_003614.2:c.395C>A

Your query was ambiguous. Multiple possible variants found:

• chr22-37824758-C-A
• chr22-37824758-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003614.2(GALR3):​c.395C>A​(p.Ala132Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000899 in 1,112,278 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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. A132V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.0e-7 (0 hom.)
• Consequence: GALR3 NM_003614.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.98

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08554727).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALR3	NM_003614.2	c.395C>A	p.Ala132Asp	missense_variant	Exon 2 of 2	ENST00000249041.3	NP_003605.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALR3	ENST00000249041.3	c.395C>A	p.Ala132Asp	missense_variant	Exon 2 of 2	1	NM_003614.2	ENSP00000249041.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.99e-7 AC: 1 AN: 1112278 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 536244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000106

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.29	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.23	N
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	0.95	N
REVEL	Benign	0.080
Sift	Benign	0.55	T
Sift4G	Benign	0.62	T
Polyphen		0.012	B
Vest4		0.076
MutPred		0.43		Loss of MoRF binding (P = 0.0387);
MVP		0.35
MPC		1.3
ClinPred		0.53	D
GERP RS		3.8
Varity_R		0.32
gMVP		0.37

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-38220765;