Genetic Variant SLC33A2:p.Gly111Ala (chr8-144509665-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_138431.3(SLC33A2):c.332G>C(p.Gly111Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,401,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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. G111D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

SLC33A2
NM_138431.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00800

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06382844).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC33A2	NM_138431.3 link	c.332G>C	p.Gly111Ala	missense_variant	Exon 1 of 5	ENST00000301327.5	NP_612440.1	Q96ES6
SLC33A2	XM_017013005.2 link	c.332G>C	p.Gly111Ala	missense_variant	Exon 1 of 4		XP_016868494.1
SLC33A2	XM_011516806.3 link	c.332G>C	p.Gly111Ala	missense_variant	Exon 1 of 5		XP_011515108.1
SLC33A2	NR_130120.2 link	n.596G>C		non_coding_transcript_exon_variant	Exon 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MFSD3	ENST00000301327.5 link	c.332G>C	p.Gly111Ala	missense_variant	Exon 1 of 5	1	NM_138431.3	ENSP00000301327.3	Q96ES6
MFSD3	ENST00000526749.1 link	n.47G>C		non_coding_transcript_exon_variant	Exon 1 of 2	2
MFSD3	ENST00000528047.5 link	n.586G>C		non_coding_transcript_exon_variant	Exon 1 of 3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.14e-7

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:

0.00

AC:

AN:

36482

South Asian (SAS)

AF:

0.0000124

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:

0.00

AC:

AN:

58316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.68

DEOGEN2

Benign

0.053

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.69

M_CAP

Benign

0.018

MetaRNN

Benign

0.064

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.51

PhyloP100

0.0080

PrimateAI

Uncertain

0.78

PROVEAN

Benign

1.2

REVEL

Benign

0.067

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.026

Vest4

0.14

MutPred

0.53

Loss of loop (P = 0.0153);

MVP

0.44

MPC

1.5

ClinPred

0.077

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.084

gMVP

0.40

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

Loading publications...

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over