2-102718551-C-A

Variant names:

• chr2-102718551-C-A
• rs764345922
• NM_032718.5:c.1294G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032718.5(SLC67A2):​c.1294G>T​(p.Val432Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,360 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. V432I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SLC67A2 NM_032718.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0150
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08156276).

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.1294G>T	p.Val432Phe	missense	Exon 6 of 6	NP_116107.3
	SLC67A2	NM_001322080.2		c.1111G>T	p.Val371Phe	missense	Exon 6 of 6	NP_001309009.1	B4DKY6
	SLC67A2	NM_001322081.2		c.1111G>T	p.Val371Phe	missense	Exon 6 of 6	NP_001309010.1	B4DKY6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFSD9	ENST00000258436.10	TSL:1 MANE Select	c.1294G>T	p.Val432Phe	missense	Exon 6 of 6	ENSP00000258436.5	Q8NBP5
	MFSD9	ENST00000939979.1		c.1291G>T	p.Val431Phe	missense	Exon 6 of 6	ENSP00000610038.1
	MFSD9	ENST00000962756.1		c.1282G>T	p.Val428Phe	missense	Exon 6 of 6	ENSP00000632815.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460360 Hom.: 0 Cov.: 34 AF XY: 0.00000413 AC XY: 3 AN XY: 726534

African (AFR) AF: 0.00 AC: 0 AN: 33410

American (AMR) AF: 0.00 AC: 0 AN: 44492

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25970

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86180

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53214

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111354

Other (OTH) AF: 0.00 AC: 0 AN: 60290

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	4.6
DANN	Benign	0.96
DEOGEN2	Benign	0.0068	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		-0.015
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.19
Sift	Benign	0.14	T
Sift4G	Benign	0.28	T
Polyphen		0.025	B
Vest4		0.31
MutPred		0.39		Loss of glycosylation at S437 (P = 0.0739)
MVP		0.39
MPC		0.053
ClinPred		0.095	T
GERP RS		0.26
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.043
gMVP		0.48
Mutation Taster		=82/18	polymorphism

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: rs764345922; hg19: chr2-103335010;