NM_138431.3:c.539T>A

Variant names:

• chr8-144509872-T-A
• NM_138431.3:c.539T>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_138431.3(SLC33A2):​c.539T>A​(p.Leu180Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: SLC33A2 NM_138431.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.464
• Publications: 0 publications found

Genes affected

SLC33A2 (HGNC:25157): (major facilitator superfamily domain containing 3) Predicted to enable solute:proton symporter activity. Predicted to be involved in proton transmembrane transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.814

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138431.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC33A2	NM_138431.3	MANE Select	c.539T>A	p.Leu180Gln	missense	Exon 1 of 5	NP_612440.1	Q96ES6
	SLC33A2	NR_130120.2		n.803T>A		non_coding_transcript_exon	Exon 1 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFSD3	ENST00000301327.5	TSL:1 MANE Select	c.539T>A	p.Leu180Gln	missense	Exon 1 of 5	ENSP00000301327.3	Q96ES6
	MFSD3	ENST00000883534.1		c.539T>A	p.Leu180Gln	missense	Exon 1 of 5	ENSP00000553593.1
	MFSD3	ENST00000526749.1	TSL:2	n.254T>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	0.0075	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.62	D
Eigen	Benign	0.030
Eigen_PC	Benign	-0.050
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.069	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		0.46
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.33
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.042	D
Polyphen		0.92	P
Vest4		0.62
MutPred		0.69		Gain of disorder (P = 0.0963)
MVP		0.68
MPC		0.20
ClinPred		0.92	D
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.34
gMVP		0.60
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr8-145735255;