22-37823563-C-G

Variant names:

• chr22-37823563-C-G
• rs78650836
• NM_003614.2:c.157C>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_003614.2(GALR3):​c.157C>G​(p.Pro53Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00528 in 1,613,694 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0037 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0054 (36 hom.)
• Consequence: GALR3 NM_003614.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.41
• Publications: 4 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005166143).
• BP6: Variant 22-37823563-C-G is Benign according to our data. Variant chr22-37823563-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2653126.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.157C>G	p.Pro53Ala	missense	Exon 1 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.157C>G	p.Pro53Ala	missense	Exon 1 of 2	ENSP00000249041.2	O60755
	GALR3	ENST00000910168.1		c.157C>G	p.Pro53Ala	missense	Exon 2 of 3	ENSP00000580227.1

Frequencies

GnomAD3 genomes AF: 0.00365 AC: 556 AN: 152198 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00157

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00209

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00497

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00569

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00378 AC: 943 AN: 249606 AF XY: 0.00405

Gnomad AFR exome AF: 0.00148

Gnomad AMR exome AF: 0.00179

Gnomad ASJ exome AF: 0.00958

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000186

Gnomad NFE exome AF: 0.00509

Gnomad OTH exome AF: 0.00525

GnomAD4 exome AF: 0.00545 AC: 7964 AN: 1461380 Hom.: 36 Cov.: 36 AF XY: 0.00553 AC XY: 4022 AN XY: 726990

African (AFR) AF: 0.00108 AC: 36 AN: 33472

American (AMR) AF: 0.00197 AC: 88 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0109 AC: 286 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00472 AC: 407 AN: 86252

European-Finnish (FIN) AF: 0.000339 AC: 18 AN: 53168

Middle Eastern (MID) AF: 0.00609 AC: 35 AN: 5744

European-Non Finnish (NFE) AF: 0.00610 AC: 6783 AN: 1111852

Other (OTH) AF: 0.00515 AC: 311 AN: 60364

GnomAD4 genome AF: 0.00365 AC: 556 AN: 152314 Hom.: 2 Cov.: 32 AF XY: 0.00325 AC XY: 242 AN XY: 74480

African (AFR) AF: 0.00156 AC: 65 AN: 41586

American (AMR) AF: 0.00209 AC: 32 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0104 AC: 36 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00497 AC: 24 AN: 4826

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10614

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00569 AC: 387 AN: 68024

Other (OTH) AF: 0.00284 AC: 6 AN: 2110

Alfa AF: 0.00550 Hom.: 3

Bravo AF: 0.00391

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.00605 AC: 52

ExAC AF: 0.00370 AC: 449

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	13
DANN	Benign	0.88
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.18
Eigen_PC	Benign	0.020
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.0052	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.91	L
PhyloP100		1.4
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.079
Sift	Benign	0.34	T
Sift4G	Benign	0.76	T
Polyphen		0.12	B
Vest4		0.26
MVP		0.56
MPC		0.064
ClinPred		0.0028	T
GERP RS		4.2
PromoterAI		0.013	Neutral
Varity_R		0.050
gMVP		0.12
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs78650836; hg19: chr22-38219570; COSMIC: COSV50763997;