Genetic Variant SLC33A2:p.Gly111Asp (chr8-144509665-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_138431.3(SLC33A2):c.332G>A(p.Gly111Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000571 in 1,401,120 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000057 ( 0 hom. )

Consequence

SLC33A2
NM_138431.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00800

Publications

0 publications found

Variant links:

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]

SLC33A2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.332G>A	p.Gly111Asp	missense	Exon 1 of 5	NP_612440.1	Q96ES6
	SLC33A2	NR_130120.2		n.596G>A		non_coding_transcript_exon	Exon 1 of 4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MFSD3	ENST00000301327.5	TSL:1 MANE Select	c.332G>A	p.Gly111Asp	missense	Exon 1 of 5	ENSP00000301327.3	Q96ES6
MFSD3	ENST00000883534.1		c.332G>A	p.Gly111Asp	missense	Exon 1 of 5	ENSP00000553593.1
MFSD3	ENST00000526749.1	TSL:2	n.47G>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000129

AC:

AN:

154476

AF XY:

0.0000119

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000826

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000230

GnomAD4 exome

AF:

0.00000571

AC:

AN:

1401120

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

692800

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32022

American (AMR)

AF:

0.00

AC:

AN:

37512

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25260

East Asian (EAS)

AF:

0.0000274

AC:

AN:

36482

South Asian (SAS)

AF:

0.00

AC:

AN:

80450

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39564

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5652

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1085862

Other (OTH)

AF:

0.000120

AC:

AN:

58316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.80

BayesDel_addAF

Benign

-0.023

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.16

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.74

M_CAP

Benign

0.069

MetaRNN

Uncertain

0.47

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.3

PhyloP100

0.0080

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-1.1

REVEL

Uncertain

0.37

Sift

Benign

0.12

Sift4G

Benign

0.076

Polyphen

0.98

Vest4

0.49

MutPred

0.74

Gain of relative solvent accessibility (P = 0.0479)

MVP

0.62

MPC

2.6

ClinPred

0.71

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.65

gMVP

0.78

Mutation Taster

=89/11

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over