rs774988366

Variant names:

• chr8-119240301-A-C
• rs774988366
• NM_052886.3:c.440A>C

Your query was ambiguous. Multiple possible variants found:

• chr8-119240301-A-C
• chr8-119240301-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_052886.3(MAL2):​c.440A>C​(p.Asn147Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N147S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAL2 NM_052886.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.87

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-AS1 (HGNC:53626): (MAL2 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAL2	NM_052886.3	c.440A>C	p.Asn147Thr	missense_variant	Exon 3 of 4	ENST00000614891.5	NP_443118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAL2	ENST00000614891.5	c.440A>C	p.Asn147Thr	missense_variant	Exon 3 of 4	1	NM_052886.3	ENSP00000479708.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248798 Hom.: 0 AF XY: 0.00000741 AC XY: 1 AN XY: 134962

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.00000886

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	22
DANN	Benign	0.64
DEOGEN2	Benign	0.16	.;.;T;.
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.68	.;.;T;T
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.69	D;D;D;D
PrimateAI	Uncertain	0.55	T
Sift4G	Uncertain	0.042	D;D;T;D
Polyphen		0.34	.;.;B;.
Vest4		0.66
MVP		0.38
GERP RS		3.1
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

LitVar

Other links and lift over

dbSNP: rs774988366; hg19: chr8-120252541;