Variant 8-119208483-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_052886.3(MAL2):c.11G>T(p.Gly4Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000345 in 1,276,022 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 0.000027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

MAL2
NM_052886.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.80

Variant links:

Genes affected

MAL2 (HGNC:13634): (mal, T cell differentiation protein 2) This gene encodes a multispan transmembrane protein belonging to the MAL proteolipid family. The protein is a component of lipid rafts and, in polarized cells, it primarily localizes to endosomal structures beneath the apical membrane. It is required for transcytosis, an intracellular transport pathway used to deliver membrane-bound proteins and exogenous cargos from the basolateral to the apical surface. [provided by RefSeq, Jul 2008]

MAL2 links:

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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=0.12718579).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAL2	NM_052886.3 linkuse as main transcript	c.11G>T	p.Gly4Val	missense_variant	1/4	ENST00000614891.5
MAL2	XM_011516807.3 linkuse as main transcript	c.11G>T	p.Gly4Val	missense_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MAL2	ENST00000614891.5 linkuse as main transcript	c.11G>T	p.Gly4Val	missense_variant	1/4	1	NM_052886.3	P1
MAL2	ENST00000522112.6 linkuse as main transcript	c.-72-13104G>T		intron_variant		4
MAL2	ENST00000534619.5 linkuse as main transcript	c.-73+390G>T		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0000265

AC:

AN:

150808

Hom.:

Cov.:

show subpopulations

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:

0.0000970

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000445

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000356

AC:

AN:

1125108

Hom.:

Cov.:

AF XY:

0.0000278

AC XY:

AN XY:

540124

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:

0.0000836

Gnomad4 NFE exome

AF:

0.0000392

Gnomad4 OTH exome

AF:

0.0000221

GnomAD4 genome

AF:

0.0000265

AC:

AN:

150914

Hom.:

Cov.:

AF XY:

0.0000271

AC XY:

AN XY:

73696

show subpopulations

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:

0.0000970

Gnomad4 NFE

AF:

0.0000445

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 15, 2023

The c.11G>T (p.G4V) alteration is located in exon 1 (coding exon 1) of the MAL2 gene. This alteration results from a G to T substitution at nucleotide position 11, causing the glycine (G) at amino acid position 4 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

Benign

0.17

BayesDel_addAF

Benign

-0.013

BayesDel_noAF

Benign

-0.26

Cadd

Uncertain

Dann

Benign

0.97

DEOGEN2

Benign

0.021

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.54

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.13

PrimateAI

Pathogenic

0.87

Sift4G

Uncertain

0.022

Polyphen

0.0

Vest4

0.28

MVP

0.47

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Varity_R

0.13

gMVP

0.61

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