2-79027835-A-G

Position:

• chr2-79027835-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The ENST00000272324.10(REG3G):​c.362A>G​(p.Glu121Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: REG3G ENST00000272324.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.900

Genes affected

REG3G (HGNC:29595): (regenerating family member 3 gamma) This gene encodes a member of the regenerating islet-derived genes (REG)3 protein family. These proteins are secreted, C-type lectins with a carbohydrate recognition domain and N-terminal signal peptide. The protein encoded by this gene is an antimicrobial lectin with activity against Gram-positive bacteria. Alternative splicing results in multiple transcript variants encoding multiple isoforms. [provided by RefSeq, Nov 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM1: In a binding_site (size 0) in uniprot entity REG3G_HUMAN
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REG3G	NM_001008387.3	c.362A>G	p.Glu121Gly	missense_variant	5/6	ENST00000272324.10	NP_001008388.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REG3G	ENST00000272324.10	c.362A>G	p.Glu121Gly	missense_variant	5/6	1	NM_001008387.3	ENSP00000272324.5
REG3G	ENST00000393897.6	c.362A>G	p.Glu121Gly	missense_variant	5/6	1		ENSP00000377475.2
REG3G	ENST00000409471.1	c.224A>G	p.Glu75Gly	missense_variant	4/5	1		ENSP00000387105.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2023

The c.362A>G (p.E121G) alteration is located in exon 5 (coding exon 4) of the REG3G gene. This alteration results from a A to G substitution at nucleotide position 362, causing the glutamic acid (E) at amino acid position 121 to be replaced by a glycine (G). 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	0.41
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.022	T;T;.
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.85	.;T;D
M_CAP	Benign	0.0076	T
MetaRNN	Uncertain	0.72	D;D;D
MetaSVM	Benign	-0.99	T
MutationAssessor	Pathogenic	3.1	M;M;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-5.3	D;D;D
REVEL	Benign	0.19
Sift	Uncertain	0.010	D;D;D
Sift4G	Uncertain	0.035	D;D;D
Polyphen		0.97	D;D;.
Vest4		0.54
MutPred		0.57		Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);.;
MVP		0.54
MPC		0.075
ClinPred		0.98	D
GERP RS		3.6
Varity_R		0.56
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr2-79254961;