chr2-102718719-C-T

Variant names:

• chr2-102718719-C-T
• rs34096572
• NM_032718.5:c.1126G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032718.5(SLC67A2):​c.1126G>A​(p.Ala376Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00312 in 1,613,890 control chromosomes in the GnomAD database, including 110 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (62 hom., cov: 33)
  • Exomes 𝑓: 0.0018 (48 hom.)
• Consequence: SLC67A2 NM_032718.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0029042363).
• BP6: Variant 2-102718719-C-T is Benign according to our data. Variant chr2-102718719-C-T is described in ClinVar as Benign. ClinVar VariationId is 775747.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0508 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.1126G>A	p.Ala376Thr	missense	Exon 6 of 6	NP_116107.3
	SLC67A2	NM_001322080.2		c.943G>A	p.Ala315Thr	missense	Exon 6 of 6	NP_001309009.1	B4DKY6
	SLC67A2	NM_001322081.2		c.943G>A	p.Ala315Thr	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>A	p.Ala376Thr	missense	Exon 6 of 6	ENSP00000258436.5	Q8NBP5
	MFSD9	ENST00000939979.1		c.1123G>A	p.Ala375Thr	missense	Exon 6 of 6	ENSP00000610038.1
	MFSD9	ENST00000962756.1		c.1114G>A	p.Ala372Thr	missense	Exon 6 of 6	ENSP00000632815.1

Frequencies

GnomAD3 genomes AF: 0.0154 AC: 2346 AN: 152208 Hom.: 62 Cov.: 33

Gnomad AFR AF: 0.0528

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00523

Gnomad ASJ AF: 0.00663

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.00956

GnomAD2 exomes AF: 0.00442 AC: 1105 AN: 249732 AF XY: 0.00352

Gnomad AFR exome AF: 0.0540

Gnomad AMR exome AF: 0.00321

Gnomad ASJ exome AF: 0.00627

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000356

Gnomad OTH exome AF: 0.00376

GnomAD4 exome AF: 0.00184 AC: 2691 AN: 1461564 Hom.: 48 Cov.: 34 AF XY: 0.00170 AC XY: 1236 AN XY: 727098

African (AFR) AF: 0.0533 AC: 1786 AN: 33480

American (AMR) AF: 0.00382 AC: 171 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00635 AC: 166 AN: 26136

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

South Asian (SAS) AF: 0.0000927 AC: 8 AN: 86258

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

Middle Eastern (MID) AF: 0.00469 AC: 27 AN: 5762

European-Non Finnish (NFE) AF: 0.000240 AC: 267 AN: 1112012

Other (OTH) AF: 0.00440 AC: 266 AN: 60392

GnomAD4 genome AF: 0.0154 AC: 2345 AN: 152326 Hom.: 62 Cov.: 33 AF XY: 0.0151 AC XY: 1125 AN XY: 74478

African (AFR) AF: 0.0527 AC: 2190 AN: 41586

American (AMR) AF: 0.00523 AC: 80 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00663 AC: 23 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000441 AC: 30 AN: 68034

Other (OTH) AF: 0.00946 AC: 20 AN: 2114

Alfa AF: 0.00661 Hom.: 61

Bravo AF: 0.0180

ESP6500AA AF: 0.0531 AC: 234

ESP6500EA AF: 0.000814 AC: 7

ExAC AF: 0.00536 AC: 651

Asia WGS AF: 0.00462 AC: 17 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000948

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.030
DANN	Benign	0.84
DEOGEN2	Benign	0.050	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.46	T
MetaRNN	Benign	0.0029	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		-0.40
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.050
Sift	Benign	0.16	T
Sift4G	Benign	0.54	T
Polyphen		0.36	B
Vest4		0.023
MVP		0.12
MPC		0.040
ClinPred		0.0032	T
GERP RS		-5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.023
gMVP		0.32
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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;