dbSNP rs33993717: SLC67A2:p.Ile288Thr (chr2-102718982-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032718.5(SLC67A2):c.863T>C(p.Ile288Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0755 in 1,614,114 control chromosomes in the GnomAD database, including 5,386 homozygotes. In-silico tool predicts 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. I288M) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.063 ( 453 hom., cov: 33)

Exomes 𝑓: 0.077 ( 4933 hom. )

Consequence

SLC67A2
NM_032718.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.67

Publications

13 publications found

Variant links:

Genes affected

SLC67A2 (HGNC:28158): (major facilitator superfamily domain containing 9) Predicted to enable transmembrane transporter activity. Predicted to be involved in transmembrane transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC67A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001899302).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC67A2	NM_032718.5 link	c.863T>C	p.Ile288Thr	missense_variant	Exon 6 of 6	ENST00000258436.10	NP_116107.3	Q8NBP5B4DKY6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MFSD9	ENST00000258436.10 link	c.863T>C	p.Ile288Thr	missense_variant	Exon 6 of 6	1	NM_032718.5	ENSP00000258436.5		Q8NBP5

Frequencies

GnomAD3 genomes

AF:

0.0626

AC:

9523

AN:

152130

Hom.:

453

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0149

Gnomad AMI

AF:

0.167

Gnomad AMR

AF:

0.0520

Gnomad ASJ

AF:

0.0874

Gnomad EAS

AF:

0.0189

Gnomad SAS

AF:

0.0153

Gnomad FIN

AF:

0.151

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0843

Gnomad OTH

AF:

0.0632

GnomAD2 exomes

AF:

0.0634

AC:

15933

AN:

251318

AF XY:

0.0633

show subpopulations

Gnomad AFR exome

AF:

0.0130

Gnomad AMR exome

AF:

0.0324

Gnomad ASJ exome

AF:

0.0905

Gnomad EAS exome

AF:

0.00767

Gnomad FIN exome

AF:

0.139

Gnomad NFE exome

AF:

0.0852

Gnomad OTH exome

AF:

0.0767

GnomAD4 exome

AF:

0.0768

AC:

112330

AN:

1461866

Hom.:

4933

Cov.:

AF XY:

0.0751

AC XY:

54619

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.0111

AC:

373

AN:

33480

American (AMR)

AF:

0.0344

AC:

1538

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0944

AC:

2466

AN:

26134

East Asian (EAS)

AF:

0.0309

AC:

1228

AN:

39686

South Asian (SAS)

AF:

0.0137

AC:

1180

AN:

86258

European-Finnish (FIN)

AF:

0.136

AC:

7245

AN:

53416

Middle Eastern (MID)

AF:

0.0460

AC:

265

AN:

5766

European-Non Finnish (NFE)

AF:

0.0844

AC:

93809

AN:

1112006

Other (OTH)

AF:

0.0700

AC:

4226

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

6912

13824

20737

27649

34561

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3296

6592

9888

13184

16480

<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

AF:

0.0626

AC:

9524

AN:

152248

Hom.:

453

Cov.:

AF XY:

0.0636

AC XY:

4736

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0148

AC:

615

AN:

41568

American (AMR)

AF:

0.0519

AC:

794

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0874

AC:

303

AN:

3468

East Asian (EAS)

AF:

0.0189

AC:

AN:

5172

South Asian (SAS)

AF:

0.0153

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.151

AC:

1604

AN:

10594

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0844

AC:

5736

AN:

68002

Other (OTH)

AF:

0.0630

AC:

133

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

456

912

1368

1824

2280

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

106

212

318

424

530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0727

Hom.:

1086

Bravo

AF:

0.0551

TwinsUK

AF:

0.0752

AC:

279

ALSPAC

AF:

0.0773

AC:

298

ESP6500AA

AF:

0.0148

AC:

ESP6500EA

AF:

0.0852

AC:

733

ExAC

AF:

0.0630

AC:

7650

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.0794

EpiControl

AF:

0.0739

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.64

MetaRNN

Benign

0.0019

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

PhyloP100

8.7

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.21

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.011

Polyphen

0.84

Vest4

0.11

MPC

0.27

ClinPred

0.028

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.18

gMVP

0.63

Mutation Taster

=89/11

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over