rs33993717

chr2-102718982-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032718.5(MFSD9):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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I288V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.063 (453 hom., cov: 33)
  • Exomes 𝑓: 0.077 (4933 hom.)
• Consequence: MFSD9 NM_032718.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.67

Genes affected

MFSD9 (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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MFSD9	NM_032718.5	c.863T>C	p.Ile288Thr	missense_variant	6/6	ENST00000258436.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MFSD9	ENST00000258436.10	c.863T>C	p.Ile288Thr	missense_variant	6/6	1	NM_032718.5	P1

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

GnomAD3 exomes AF: 0.0634 AC: 15933 AN: 251318 Hom.: 748 AF XY: 0.0633 AC XY: 8607 AN XY: 135892

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 SAS exome AF: 0.0122

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

Gnomad4 AFR exome AF: 0.0111

Gnomad4 AMR exome AF: 0.0344

Gnomad4 ASJ exome AF: 0.0944

Gnomad4 EAS exome AF: 0.0309

Gnomad4 SAS exome AF: 0.0137

Gnomad4 FIN exome AF: 0.136

Gnomad4 NFE exome AF: 0.0844

Gnomad4 OTH exome AF: 0.0700

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

Gnomad4 AFR AF: 0.0148

Gnomad4 AMR AF: 0.0519

Gnomad4 ASJ AF: 0.0874

Gnomad4 EAS AF: 0.0189

Gnomad4 SAS AF: 0.0153

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.0844

Gnomad4 OTH AF: 0.0630

Alfa AF: 0.0771 Hom.: 826

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 v4.3

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
MutationTaster	Benign	1.0	N
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

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

LitVar

Other links and lift over

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