13-35475319-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005584.5(MAB21L1):c.820A>G(p.Met274Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00142 in 1,614,018 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00089 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0015 ( 5 hom. )

Consequence

MAB21L1
NM_005584.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 8.02

Variant links:

Genes affected

MAB21L1 (HGNC:6757): (mab-21 like 1) This gene is similar to the MAB-21 cell fate-determining gene found in C. elegans. It may be involved in eye and cerebellum development, and it has been proposed that expansion of a trinucleotide repeat region in the 5' UTR may play a role in a variety of psychiatric disorders. [provided by RefSeq, Oct 2008]

MAB21L1 links:

NBEA (HGNC:7648): (neurobeachin) This gene encodes a member of a large, diverse group of A-kinase anchor proteins that target the activity of protein kinase A to specific subcellular sites by binding to its type II regulatory subunits. Brain-specific expression and coat protein-like membrane recruitment of a highly similar protein in mouse suggest an involvement in neuronal post-Golgi membrane traffic. Mutations in this gene may be associated with a form of autism. This gene and its expression are frequently disrupted in patients with multiple myeloma. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional transcript variants may exist, but their full-length nature has not been determined.[provided by RefSeq, Feb 2011]

NBEA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06410292).

BP6

Variant 13-35475319-T-C is Benign according to our data. Variant chr13-35475319-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3045100.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAB21L1	NM_005584.5 link	c.820A>G	p.Met274Val	missense_variant	Exon 1 of 1	ENST00000379919.6	NP_005575.1	Q13394F1T0A2B2R805
NBEA	NM_001385012.1 link	c.6585+2783T>C		intron_variant	Intron 41 of 58	ENST00000379939.7	NP_001371941.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAB21L1	ENST00000379919.6 link	c.820A>G	p.Met274Val	missense_variant	Exon 1 of 1	6	NM_005584.5	ENSP00000369251.4		Q13394
NBEA	ENST00000379939.7 link	c.6585+2783T>C		intron_variant	Intron 41 of 58	5	NM_001385012.1	ENSP00000369271.2		Q5T321

Frequencies

GnomAD3 genomes

AF:

0.000895

AC:

136

AN:

152012

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000917

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00154

Gnomad OTH

AF:

0.000959

GnomAD3 exomes

AF:

0.000855

AC:

215

AN:

251482

Hom.:

AF XY:

0.000883

AC XY:

120

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000434

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.000416

Gnomad NFE exome

AF:

0.00158

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00148

AC:

2163

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00142

AC XY:

1035

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000470

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000371

Gnomad4 FIN exome

AF:

0.000543

Gnomad4 NFE exome

AF:

0.00180

Gnomad4 OTH exome

AF:

0.00123

GnomAD4 genome

AF:

0.000894

AC:

136

AN:

152130

Hom.:

Cov.:

AF XY:

0.000901

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.000916

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00154

Gnomad4 OTH

AF:

0.000949

Alfa

AF:

0.00140

Hom.:

Bravo

AF:

0.000839

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.000997

AC:

121

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00147

EpiControl

AF:

0.00142

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

MAB21L1-related disorder

Benign:1

Jul 18, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

NBEA: BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

0.0

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.12

Eigen

Benign

0.075

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.014

MetaRNN

Benign

0.064

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

PROVEAN

Benign

-1.0

REVEL

Benign

0.28

Sift

Benign

0.046

Sift4G

Benign

0.12

Polyphen

0.0010

Vest4

0.75

MVP

0.49

MPC

0.71

ClinPred

0.049

GERP RS

5.8

Varity_R

0.66

gMVP

0.68

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