NM_001004317.4:c.62C>A

Variant summary

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

The NM_001004317.4(LIN28B):​c.62C>A​(p.Ala21Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

LIN28B
NM_001004317.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.81
Variant links:
Genes affected
LIN28B (HGNC:32207): (lin-28 homolog B) The protein encoded by this gene belongs to the lin-28 family, which is characterized by the presence of a cold-shock domain and a pair of CCHC zinc finger domains. This gene is highly expressed in testis, fetal liver, placenta, and in primary human tumors and cancer cell lines. It is negatively regulated by microRNAs that target sites in the 3' UTR, and overexpression of this gene in primary tumors is linked to the repression of let-7 family of microRNAs and derepression of let-7 targets, which facilitates cellular transformation. [provided by RefSeq, Jun 2012]

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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=0.11068502).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LIN28BNM_001004317.4 linkc.62C>A p.Ala21Glu missense_variant Exon 2 of 4 ENST00000345080.5 NP_001004317.1 Q6ZN17-1
LIN28BNM_001410939.1 linkc.86C>A p.Ala29Glu missense_variant Exon 3 of 5 NP_001397868.1
LIN28BXM_006715477.3 linkc.119C>A p.Ala40Glu missense_variant Exon 3 of 5 XP_006715540.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LIN28BENST00000345080.5 linkc.62C>A p.Ala21Glu missense_variant Exon 2 of 4 1 NM_001004317.4 ENSP00000344401.4 Q6ZN17-1
LIN28BENST00000637759.1 linkc.86C>A p.Ala29Glu missense_variant Exon 3 of 5 5 ENSP00000490468.1 A0A1B0GVD3
LIN28BENST00000635857.1 linkc.119C>A p.Ala40Glu missense_variant Exon 4 of 6 5 ENSP00000489735.1 A0A1B0GTK2

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
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 10, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.62C>A (p.A21E) alteration is located in exon 2 (coding exon 2) of the LIN28B gene. This alteration results from a C to A substitution at nucleotide position 62, causing the alanine (A) at amino acid position 21 to be replaced by a glutamic acid (E). 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
0.078
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
19
DANN
Benign
0.92
DEOGEN2
Benign
0.017
.;.;T
Eigen
Benign
-0.38
Eigen_PC
Benign
-0.16
FATHMM_MKL
Benign
0.27
N
LIST_S2
Benign
0.77
T;T;T
M_CAP
Benign
0.0011
T
MetaRNN
Benign
0.11
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.69
.;.;N
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-0.94
.;.;N
REVEL
Benign
0.21
Sift
Benign
0.34
.;.;T
Sift4G
Benign
0.89
.;.;T
Polyphen
0.0
.;.;B
Vest4
0.17
MutPred
0.23
.;.;Gain of solvent accessibility (P = 0.0068);
MVP
0.17
MPC
0.69
ClinPred
0.67
D
GERP RS
3.4
Varity_R
0.16
gMVP
0.17

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
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: chr6-105406025; API