3-108757063-A-T

Variant names:

• chr3-108757063-A-T
• NM_032579.3:c.123T>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_032579.3(RETNLB):​c.123T>A​(p.Ser41Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RETNLB NM_032579.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.203

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05503729).
• BP6: Variant 3-108757063-A-T is Benign according to our data. Variant chr3-108757063-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 3788360.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RETNLB	NM_032579.3	c.123T>A	p.Ser41Arg	missense_variant	Exon 1 of 3	ENST00000295755.7	NP_115968.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RETNLB	ENST00000295755.7	c.123T>A	p.Ser41Arg	missense_variant	Exon 1 of 3	1	NM_032579.3	ENSP00000295755.6
RETNLB	ENST00000482939.1	n.-48T>A		upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Dec 25, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.5
DANN	Benign	0.49
DEOGEN2	Benign	0.20	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0024	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.66	N
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.079
Sift	Benign	0.50	T
Sift4G	Benign	0.64	T
Polyphen		0.0	B
Vest4		0.099
MutPred		0.44		Loss of ubiquitination at K36 (P = 0.0368);
MVP		0.030
MPC		0.020
ClinPred		0.11	T
GERP RS		1.8
Varity_R		0.061
gMVP		0.18

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: chr3-108475910;