8-144509728-T-A

Variant names:

• chr8-144509728-T-A
• NM_138431.3:c.395T>A

Variant summary

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

The NM_138431.3(MFSD3):​c.395T>A​(p.Leu132Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: MFSD3 NM_138431.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.52

Genes affected

MFSD3 (HGNC:25157): (major facilitator superfamily domain containing 3) Predicted to enable solute:proton symporter activity. Predicted to be involved in proton 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 rank	MANE	Protein	UniProt
MFSD3	NM_138431.3	c.395T>A	p.Leu132Gln	missense_variant	Exon 1 of 5	ENST00000301327.5	NP_612440.1
MFSD3	XM_017013005.2	c.395T>A	p.Leu132Gln	missense_variant	Exon 1 of 4		XP_016868494.1
MFSD3	XM_011516806.3	c.395T>A	p.Leu132Gln	missense_variant	Exon 1 of 5		XP_011515108.1
MFSD3	NR_130120.2	n.659T>A		non_coding_transcript_exon_variant	Exon 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MFSD3	ENST00000301327.5	c.395T>A	p.Leu132Gln	missense_variant	Exon 1 of 5	1	NM_138431.3	ENSP00000301327.3
MFSD3	ENST00000526749.1	n.110T>A		non_coding_transcript_exon_variant	Exon 1 of 2	2
MFSD3	ENST00000528047.5	n.649T>A		non_coding_transcript_exon_variant	Exon 1 of 3	3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.395T>A (p.L132Q) alteration is located in exon 1 (coding exon 1) of the MFSD3 gene. This alteration results from a T to A substitution at nucleotide position 395, causing the leucine (L) at amino acid position 132 to be replaced by a glutamine (Q). 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	0.19
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.40	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.85	T
M_CAP	Uncertain	0.21	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.66
MutPred		0.53		Gain of solvent accessibility (P = 0.001);
MVP		0.68
MPC		0.20
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.78
gMVP		0.59

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: chr8-145735111;