2-110115780-C-A

Variant summary

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

The NM_005434.5(MALL):​c.13G>T​(p.Asp5Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000894 in 1,118,342 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 30)
Exomes 𝑓: 8.9e-7 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

MALL
NM_005434.5 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.119
Variant links:
Genes affected
MALL (HGNC:6818): (mal, T cell differentiation protein like) This gene encodes an element of the machinery for raft-mediated trafficking in endothelial cells. The encoded protein, a member of the MAL proteolipid family, predominantly localizes in glycolipid- and cholesterol-enriched membrane (GEM) rafts. It interacts with caveolin-1. [provided by RefSeq, Jul 2008]

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=0.1833967).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MALLNM_005434.5 linkc.13G>T p.Asp5Tyr missense_variant Exon 1 of 4 ENST00000272462.3 NP_005425.1 Q13021
MALLNM_001371560.1 linkc.13G>T p.Asp5Tyr missense_variant Exon 1 of 3 NP_001358489.1
MALLNM_001371559.1 linkc.93+2237G>T intron_variant Intron 1 of 3 NP_001358488.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MALLENST00000272462.3 linkc.13G>T p.Asp5Tyr missense_variant Exon 1 of 4 1 NM_005434.5 ENSP00000272462.2 Q13021
MALLENST00000427178.1 linkc.13G>T p.Asp5Tyr missense_variant Exon 1 of 2 1 ENSP00000400518.1 C9IZ55
MALLENST00000424988.1 linkn.13G>T non_coding_transcript_exon_variant Exon 1 of 5 3 ENSP00000394792.1 F8WE57

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
151470
Hom.:
0
Cov.:
30
FAILED QC
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
8.94e-7
AC:
1
AN:
1118342
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
531012
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:
0.00
Gnomad4 NFE exome
AF:
0.00000107
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
151582
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
74032
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:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
May 02, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.13G>T (p.D5Y) alteration is located in exon 1 (coding exon 1) of the MALL gene. This alteration results from a G to T substitution at nucleotide position 13, causing the aspartic acid (D) at amino acid position 5 to be replaced by a tyrosine (Y). 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
0.13
BayesDel_addAF
Benign
-0.092
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
22
DANN
Benign
0.93
DEOGEN2
Benign
0.10
T;.
Eigen
Benign
-0.43
Eigen_PC
Benign
-0.50
FATHMM_MKL
Benign
0.14
N
LIST_S2
Benign
0.79
T;T
M_CAP
Benign
0.039
D
MetaRNN
Benign
0.18
T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Uncertain
2.2
M;.
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
-1.1
N;D
REVEL
Benign
0.12
Sift
Uncertain
0.020
D;D
Sift4G
Uncertain
0.043
D;D
Polyphen
0.98
D;.
Vest4
0.32
MutPred
0.20
Gain of catalytic residue at D5 (P = 0.0372);Gain of catalytic residue at D5 (P = 0.0372);
MVP
0.40
MPC
2.4
ClinPred
0.88
D
GERP RS
3.6
Varity_R
0.17
gMVP
0.54

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-110873357; API