8-144509734-C-G

Position:

• chr8-144509734-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_138431.3(MFSD3):​c.401C>G​(p.Pro134Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 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: 0.228

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]

MFSD3 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33607522).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFSD3	NM_138431.3	c.401C>G	p.Pro134Arg	missense_variant	1/5	ENST00000301327.5	NP_612440.1
MFSD3	XM_017013005.2	c.401C>G	p.Pro134Arg	missense_variant	1/4		XP_016868494.1
MFSD3	XM_011516806.3	c.401C>G	p.Pro134Arg	missense_variant	1/5		XP_011515108.1
MFSD3	NR_130120.2	n.665C>G		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFSD3	ENST00000301327.5	c.401C>G	p.Pro134Arg	missense_variant	1/5	1	NM_138431.3	ENSP00000301327.3
MFSD3	ENST00000526749.1	n.116C>G		non_coding_transcript_exon_variant	1/2	2
MFSD3	ENST00000528047.5	n.655C>G		non_coding_transcript_exon_variant	1/3	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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 29, 2022

The c.401C>G (p.P134R) alteration is located in exon 1 (coding exon 1) of the MFSD3 gene. This alteration results from a C to G substitution at nucleotide position 401, causing the proline (P) at amino acid position 134 to be replaced by an arginine (R). 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	0.095
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.070	T
Eigen	Benign	0.17
Eigen_PC	Benign	0.057
FATHMM_MKL	Benign	0.098	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	1.9	L
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.21
Sift	Benign	0.19	T
Sift4G	Benign	0.081	T
Polyphen		1.0	D
Vest4		0.44
MutPred		0.49		Gain of methylation at P134 (P = 0.0071);
MVP		0.73
MPC		0.20
ClinPred		0.70	D
GERP RS		4.1
Varity_R		0.11
gMVP		0.62

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: chr8-145735117;