2-102718919-G-A

Position:

• chr2-102718919-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032718.5(MFSD9):​c.926C>T​(p.Ala309Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MFSD9 NM_032718.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.21

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFSD9	NM_032718.5	c.926C>T	p.Ala309Val	missense_variant	6/6	ENST00000258436.10	NP_116107.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFSD9	ENST00000258436.10	c.926C>T	p.Ala309Val	missense_variant	6/6	1	NM_032718.5	ENSP00000258436	P1
MFSD9	ENST00000411991.5	c.*731C>T		3_prime_UTR_variant, NMD_transcript_variant	7/7	1		ENSP00000392605
MFSD9	ENST00000437075.6	c.*727C>T		3_prime_UTR_variant, NMD_transcript_variant	7/7	5		ENSP00000414870
MFSD9	ENST00000438943.5	c.*762C>T		3_prime_UTR_variant, NMD_transcript_variant	7/7	5		ENSP00000408630

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 29, 2024

The c.926C>T (p.A309V) alteration is located in exon 6 (coding exon 6) of the MFSD9 gene. This alteration results from a C to T substitution at nucleotide position 926, causing the alanine (A) at amino acid position 309 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.092	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.9	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.21
Sift	Benign	0.12	T
Sift4G	Benign	0.47	T
Polyphen		0.91	P
Vest4		0.62
MutPred		0.59		Gain of catalytic residue at A309 (P = 0.1099);
MVP		0.62
MPC		0.15
ClinPred		0.94	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.10
gMVP		0.70

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-103335378;