Variant 1-116124189-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_152367.3(MAB21L3):c.313C>G(p.Arg105Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R105Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

MAB21L3
NM_152367.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.33

Variant links:

Genes affected

MAB21L3 (HGNC:26787): (mab-21 like 3)

MAB21L3 links:

MAB21L3 (HGNC:):

MAB21L3 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=0.2710604).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAB21L3	NM_152367.3 linkuse as main transcript	c.313C>G	p.Arg105Gly	missense_variant	5/8	ENST00000369500.4	NP_689580.2	Q8N8X9
MAB21L3	XM_047444823.1 linkuse as main transcript	c.313C>G	p.Arg105Gly	missense_variant	4/7		XP_047300779.1
LOC105378918	XR_947725.2 linkuse as main transcript	n.-28G>C		upstream_gene_variant
LOC105378918	XR_947726.2 linkuse as main transcript	n.-28G>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MAB21L3	ENST00000369500.4 linkuse as main transcript	c.313C>G	p.Arg105Gly	missense_variant	5/8	2	NM_152367.3	ENSP00000358512.3	Q8N8X9
MAB21L3	ENST00000683341.1 linkuse as main transcript	c.313C>G	p.Arg105Gly	missense_variant	4/7			ENSP00000508049.1	Q8N8X9
MAB21L3	ENST00000684484.1 linkuse as main transcript	c.313C>G	p.Arg105Gly	missense_variant	4/7			ENSP00000506754.1	Q8N8X9
MAB21L3	ENST00000464946.1 linkuse as main transcript	n.151C>G		non_coding_transcript_exon_variant	2/4	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251440

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135914

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:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

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

Oct 06, 2021

The c.313C>G (p.R105G) alteration is located in exon 4 (coding exon 3) of the MAB21L3 gene. This alteration results from a C to G substitution at nucleotide position 313, causing the arginine (R) at amino acid position 105 to be replaced by a glycine (G). 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

0.12

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.065

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.50

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.64

M_CAP

Benign

0.011

MetaRNN

Benign

0.27

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

MutationTaster

Benign

0.83

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.9

REVEL

Benign

0.17

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.015

Polyphen

0.010

Vest4

0.52

MVP

0.27

MPC

0.11

ClinPred

0.33

GERP RS

3.2

Varity_R

0.15

gMVP

0.67

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