Genetic Variant MALL:p.Asp5Tyr (chr2-110115780-C-A) – ACMG Classification: Uncertain_significance (0 pts)

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

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]

MALL 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=0.1833967).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MALL	NM_005434.5 link	c.13G>T	p.Asp5Tyr	missense_variant	Exon 1 of 4	ENST00000272462.3	NP_005425.1	Q13021
MALL	NM_001371560.1 link	c.13G>T	p.Asp5Tyr	missense_variant	Exon 1 of 3		NP_001358489.1
MALL	NM_001371559.1 link	c.93+2237G>T		intron_variant	Intron 1 of 3		NP_001358488.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MALL	ENST00000272462.3 link	c.13G>T	p.Asp5Tyr	missense_variant	Exon 1 of 4	1	NM_005434.5	ENSP00000272462.2	Q13021
MALL	ENST00000427178.1 link	c.13G>T	p.Asp5Tyr	missense_variant	Exon 1 of 2	1		ENSP00000400518.1	C9IZ55
MALL	ENST00000424988.1 link	n.13G>T		non_coding_transcript_exon_variant	Exon 1 of 5	3		ENSP00000394792.1	F8WE57

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151470

Hom.:

Cov.:

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:

AN:

1118342

Hom.:

Cov.:

AF XY:

0.00

AC XY:

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:

AN:

151582

Hom.:

Cov.:

AF XY:

0.00

AC XY:

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

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.10

T;.

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.039

MetaRNN

Benign

0.18

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.2

M;.

PrimateAI

Uncertain

0.56

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over