Variant 16-87402990-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_022818.5(MAP1LC3B):c.271G>A(p.Val91Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000731 in 1,613,922 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 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000078 ( 0 hom. )

Consequence

MAP1LC3B
NM_022818.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.92

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:

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=0.24428064).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP1LC3B	NM_022818.5 linkuse as main transcript	c.271G>A	p.Val91Ile	missense_variant	4/4	ENST00000268607.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MAP1LC3B	ENST00000268607.10 linkuse as main transcript	c.271G>A	p.Val91Ile	missense_variant	4/4	1	NM_022818.5	P1
MAP1LC3B	ENST00000564844.1 linkuse as main transcript	c.*1005G>A		3_prime_UTR_variant, NMD_transcript_variant	5/5	1
MAP1LC3B	ENST00000570189.5 linkuse as main transcript	c.*216G>A		3_prime_UTR_variant, NMD_transcript_variant	5/5	1
MAP1LC3B	ENST00000650688.1 linkuse as main transcript	c.271G>A	p.Val91Ile	missense_variant	5/5			P1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152206

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000875

AC:

AN:

251334

Hom.:

AF XY:

0.0000957

AC XY:

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000150

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000780

AC:

114

AN:

1461716

Hom.:

Cov.:

AF XY:

0.0000756

AC XY:

AN XY:

727162

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000926

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74358

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:

0.0000588

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000529

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.0000988

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

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

Jun 22, 2021

The c.271G>A (p.V91I) alteration is located in exon 4 (coding exon 4) of the MAP1LC3B gene. This alteration results from a G to A substitution at nucleotide position 271, causing the valine (V) at amino acid position 91 to be replaced by an isoleucine (I). 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

-0.23

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.77

M_CAP

Benign

0.0098

MetaRNN

Benign

0.24

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.66

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.58

REVEL

Benign

0.17

Sift

Benign

0.17

Sift4G

Benign

0.27

Polyphen

0.077

Vest4

0.46

MVP

0.76

MPC

0.63

ClinPred

0.047

GERP RS

5.5

Varity_R

0.21

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