NM_032718.5:c.863T>C

Variant names:

• chr2-102718982-A-G
• rs33993717
• NM_032718.5:c.863T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.67
• Publications: 13 publications found

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032718.5. 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
	SLC67A2	NM_032718.5	MANE Select	c.863T>C	p.Ile288Thr	missense	Exon 6 of 6	NP_116107.3
	SLC67A2	NM_001322080.2		c.680T>C	p.Ile227Thr	missense	Exon 6 of 6	NP_001309009.1
	SLC67A2	NM_001322081.2		c.680T>C	p.Ile227Thr	missense	Exon 6 of 6	NP_001309010.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFSD9	ENST00000258436.10	TSL:1 MANE Select	c.863T>C	p.Ile288Thr	missense	Exon 6 of 6	ENSP00000258436.5
	MFSD9	ENST00000411991.5	TSL:1	n.*668T>C		non_coding_transcript_exon	Exon 7 of 7	ENSP00000392605.1
	MFSD9	ENST00000411991.5	TSL:1	n.*668T>C		3_prime_UTR	Exon 7 of 7	ENSP00000392605.1

Frequencies

GnomAD3 genomes AF: 0.0626 AC: 9523 AN: 152130 Hom.: 453 Cov.: 33

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

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.: 34 AF XY: 0.0751 AC XY: 54619 AN XY: 727234

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

GnomAD4 genome AF: 0.0626 AC: 9524 AN: 152248 Hom.: 453 Cov.: 33 AF XY: 0.0636 AC XY: 4736 AN XY: 74454

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: 98 AN: 5172

South Asian (SAS) AF: 0.0153 AC: 74 AN: 4828

European-Finnish (FIN) AF: 0.151 AC: 1604 AN: 10594

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0844 AC: 5736 AN: 68002

Other (OTH) AF: 0.0630 AC: 133 AN: 2110

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: 65

ESP6500EA AF: 0.0852 AC: 733

ExAC AF: 0.0630 AC: 7650

Asia WGS AF: 0.0180 AC: 62 AN: 3478

EpiCase AF: 0.0794

EpiControl AF: 0.0739

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.64	T
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		8.7
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.21
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.011	D
Polyphen		0.84	P
Vest4		0.11
MPC		0.27
ClinPred		0.028	T
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)

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

Other links and lift over

dbSNP: rs33993717; hg19: chr2-103335441; COSMIC: COSV51495970; COSMIC: COSV51495970;