chr2-102718719-C-A

Variant names:

• chr2-102718719-C-A
• rs34096572
• NM_032718.5:c.1126G>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.1126G>T​(p.Ala376Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,564 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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. A376T) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: SLC67A2 NM_032718.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.401
• Publications: 7 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=0.0761964).

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.1126G>T	p.Ala376Ser	missense	Exon 6 of 6	NP_116107.3
	SLC67A2	NM_001322080.2		c.943G>T	p.Ala315Ser	missense	Exon 6 of 6	NP_001309009.1	B4DKY6
	SLC67A2	NM_001322081.2		c.943G>T	p.Ala315Ser	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.1126G>T	p.Ala376Ser	missense	Exon 6 of 6	ENSP00000258436.5	Q8NBP5
	MFSD9	ENST00000939979.1		c.1123G>T	p.Ala375Ser	missense	Exon 6 of 6	ENSP00000610038.1
	MFSD9	ENST00000962756.1		c.1114G>T	p.Ala372Ser	missense	Exon 6 of 6	ENSP00000632815.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461564 Hom.: 0 Cov.: 34 AF XY: 0.00000550 AC XY: 4 AN XY: 727098

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53100

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000629 AC: 7 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 61

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.024
DANN	Benign	0.58
DEOGEN2	Benign	0.066	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.087	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		-0.40
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.035
Sift	Benign	0.36	T
Sift4G	Benign	0.69	T
Polyphen		0.049	B
Vest4		0.036
MutPred		0.36		Gain of disorder (P = 0.1473)
MVP		0.16
MPC		0.041
ClinPred		0.077	T
GERP RS		-5.2
Varity_R		0.035
gMVP		0.35
Mutation Taster		=99/1	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: rs34096572; hg19: chr2-103335178;