3-108756560-C-A

Variant summary

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

The NM_032579.3(RETNLB):​c.156G>T​(p.Lys52Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,244 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.0000014 ( 0 hom. )

Consequence

RETNLB
NM_032579.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00500
Variant links:
Genes affected
RETNLB (HGNC:20388): (resistin like beta) Predicted to enable hormone activity. Involved in epithelial cell proliferation. Predicted to be located in extracellular region. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

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=0.10628933).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RETNLBNM_032579.3 linkc.156G>T p.Lys52Asn missense_variant Exon 2 of 3 ENST00000295755.7 NP_115968.1 Q9BQ08

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RETNLBENST00000295755.7 linkc.156G>T p.Lys52Asn missense_variant Exon 2 of 3 1 NM_032579.3 ENSP00000295755.6 Q9BQ08
RETNLBENST00000482939.1 linkn.225G>T non_coding_transcript_exon_variant Exon 2 of 5 3

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152104
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251464
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135904
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461140
Hom.:
0
Cov.:
29
AF XY:
0.00000138
AC XY:
1
AN XY:
726938
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152104
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74294
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000478
Bravo
AF:
0.0000227

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 15, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.156G>T (p.K52N) alteration is located in exon 2 (coding exon 2) of the RETNLB gene. This alteration results from a G to T substitution at nucleotide position 156, causing the lysine (K) at amino acid position 52 to be replaced by an asparagine (N). 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
0.19
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.76
CADD
Benign
2.6
DANN
Benign
0.65
DEOGEN2
Benign
0.062
T
Eigen
Benign
-0.94
Eigen_PC
Benign
-0.98
FATHMM_MKL
Benign
0.062
N
LIST_S2
Benign
0.34
T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.76
N
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-0.31
N
REVEL
Benign
0.039
Sift
Benign
0.59
T
Sift4G
Benign
0.54
T
Polyphen
0.22
B
Vest4
0.13
MutPred
0.45
Loss of ubiquitination at K52 (P = 0.0118);
MVP
0.040
MPC
0.023
ClinPred
0.075
T
GERP RS
2.3
Varity_R
0.044
gMVP
0.16

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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.

Other links and lift over

dbSNP: rs1435790537; hg19: chr3-108475407; API