Variant 16-87392459-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_022818.5(MAP1LC3B):c.32G>T(p.Arg11Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000124 in 1,366,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000099 ( 0 hom. )

Consequence

MAP1LC3B
NM_022818.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.80

Variant links:

Genes affected

MAP1LC3B (HGNC:13352): (microtubule associated protein 1 light chain 3 beta) The product of this gene is a subunit of neuronal microtubule-associated MAP1A and MAP1B proteins, which are involved in microtubule assembly and important for neurogenesis. Studies on the rat homolog implicate a role for this gene in autophagy, a process that involves the bulk degradation of cytoplasmic component. [provided by RefSeq, Jul 2008]

MAP1LC3B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31358594).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP1LC3B	NM_022818.5 linkuse as main transcript	c.32G>T	p.Arg11Leu	missense_variant	1/4	ENST00000268607.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP1LC3B	ENST00000268607.10 linkuse as main transcript	c.32G>T	p.Arg11Leu	missense_variant	1/4	1	NM_022818.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

151906

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:

0.0000736

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000988

AC:

AN:

1214662

Hom.:

Cov.:

AF XY:

0.00000673

AC XY:

AN XY:

594010

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:

0.0000335

Gnomad4 NFE exome

AF:

0.0000110

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152014

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74318

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:

0.0000736

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000302

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

Aug 12, 2021

The c.32G>T (p.R11L) alteration is located in exon 1 (coding exon 1) of the MAP1LC3B gene. This alteration results from a G to T substitution at nucleotide position 32, causing the arginine (R) at amino acid position 11 to be replaced by a leucine (L). 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

Pathogenic

0.96

BayesDel_addAF

Uncertain

0.015

BayesDel_noAF

Benign

-0.22

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.48

T;.

Eigen

Benign

-0.12

Eigen_PC

Benign

0.0056

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.88

D;D

M_CAP

Pathogenic

0.41

MetaRNN

Benign

0.31

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.87

PROVEAN

Pathogenic

-4.4

D;D

REVEL

Benign

0.23

Sift

Uncertain

0.027

D;T

Sift4G

Benign

0.28

T;T

Polyphen

0.0010

B;.

Vest4

0.32

MutPred

0.43

Loss of MoRF binding (P = 0.019);Loss of MoRF binding (P = 0.019);

MVP

0.64

MPC

0.96

ClinPred

1.0

GERP RS

3.6

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.88

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