13-35476122-G-A

Variant summary

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

The NM_005584.5(MAB21L1):​c.17C>T​(p.Ala6Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000156 in 1,614,116 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 0.00015 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

MAB21L1
NM_005584.5 missense

Scores

2
7
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 10.0
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]
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]

Genome browser will be placed here

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=0.3590443).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MAB21L1NM_005584.5 linkuse as main transcriptc.17C>T p.Ala6Val missense_variant 1/1 ENST00000379919.6 NP_005575.1
NBEANM_001385012.1 linkuse as main transcriptc.6585+3586G>A intron_variant ENST00000379939.7 NP_001371941.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MAB21L1ENST00000379919.6 linkuse as main transcriptc.17C>T p.Ala6Val missense_variant 1/1 NM_005584.5 ENSP00000369251 P1
NBEAENST00000379939.7 linkuse as main transcriptc.6585+3586G>A intron_variant 5 NM_001385012.1 ENSP00000369271

Frequencies

GnomAD3 genomes
AF:
0.000151
AC:
23
AN:
152190
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
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:
0.000279
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000167
AC:
42
AN:
251320
Hom.:
1
AF XY:
0.000206
AC XY:
28
AN XY:
135874
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000578
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:
0.000352
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000157
AC:
229
AN:
1461808
Hom.:
0
Cov.:
32
AF XY:
0.000176
AC XY:
128
AN XY:
727184
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000196
Gnomad4 OTH exome
AF:
0.000132
GnomAD4 genome
AF:
0.000151
AC:
23
AN:
152308
Hom.:
0
Cov.:
31
AF XY:
0.000134
AC XY:
10
AN XY:
74466
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000279
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000348
Hom.:
0
Bravo
AF:
0.000155
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000465
AC:
4
ExAC
AF:
0.000189
AC:
23
EpiCase
AF:
0.000600
EpiControl
AF:
0.000415

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 17, 2023The c.17C>T (p.A6V) alteration is located in exon 1 (coding exon 1) of the MAB21L1 gene. This alteration results from a C to T substitution at nucleotide position 17, causing the alanine (A) at amino acid position 6 to be replaced by a valine (V). 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
Uncertain
0.36
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.12
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.25
T
Eigen
Uncertain
0.22
Eigen_PC
Uncertain
0.43
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.97
D
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.36
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.55
N
MutationTaster
Benign
1.0
D;D;D;D;D
PROVEAN
Benign
-1.4
N
REVEL
Uncertain
0.30
Sift
Uncertain
0.019
D
Sift4G
Uncertain
0.056
T
Polyphen
0.075
B
Vest4
0.65
MVP
0.56
MPC
0.75
ClinPred
0.13
T
GERP RS
5.8
Varity_R
0.65
gMVP
0.48

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.

Other links and lift over

dbSNP: rs141975683; hg19: chr13-36050259; API