Variant 2-79027880-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000272324.10(REG3G):c.407A>C(p.Asn136Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000595 in 1,613,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

REG3G
ENST00000272324.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.796

Variant links:

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]

REG3G links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.15651354).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REG3G	NM_001008387.3 linkuse as main transcript	c.407A>C	p.Asn136Thr	missense_variant	5/6	ENST00000272324.10	NP_001008388.1	Q6UW15-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
REG3G	ENST00000272324.10 linkuse as main transcript	c.407A>C	p.Asn136Thr	missense_variant	5/6	1	NM_001008387.3	ENSP00000272324.5	Q6UW15-1
REG3G	ENST00000393897.6 linkuse as main transcript	c.407A>C	p.Asn136Thr	missense_variant	5/6	1		ENSP00000377475.2	Q6UW15-1
REG3G	ENST00000409471.1 linkuse as main transcript	c.269A>C	p.Asn90Thr	missense_variant	4/5	1		ENSP00000387105.1	Q6UW15-2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

151956

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

251134

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135720

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000529

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000636

AC:

AN:

1461820

Hom.:

Cov.:

AF XY:

0.0000536

AC XY:

AN XY:

727208

show subpopulations

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:

0.0000818

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000197

AC:

AN:

151956

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74212

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000330

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

May 31, 2023

The c.407A>C (p.N136T) alteration is located in exon 5 (coding exon 4) of the REG3G gene. This alteration results from a A to C substitution at nucleotide position 407, causing the asparagine (N) at amino acid position 136 to be replaced by a threonine (T). 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

Benign

0.18

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.60

CADD

Benign

3.1

DANN

Benign

0.94

DEOGEN2

Benign

0.025

T;T;.

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.54

.;T;T

M_CAP

Benign

0.0033

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.6

M;M;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-3.7

D;D;D

REVEL

Benign

0.012

Sift

Benign

0.10

T;T;T

Sift4G

Uncertain

0.059

T;T;T

Polyphen

0.049

B;B;.

Vest4

0.27

MutPred

0.36

Gain of ubiquitination at K135 (P = 0.0961);Gain of ubiquitination at K135 (P = 0.0961);.;

MVP

0.33

MPC

0.013

ClinPred

0.64

GERP RS

0.96

Varity_R

0.14

gMVP

0.089

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