Variant 8-144510629-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000301327.5(MFSD3):c.862C>T(p.Arg288Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000574 in 1,568,142 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000054 ( 0 hom. )

Consequence

MFSD3
ENST00000301327.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.36

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.062052846).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MFSD3	NM_138431.3 linkuse as main transcript	c.862C>T	p.Arg288Cys	missense_variant	3/5	ENST00000301327.5	NP_612440.1
MFSD3	XM_017013005.2 linkuse as main transcript	c.862C>T	p.Arg288Cys	missense_variant	3/4		XP_016868494.1
MFSD3	XM_011516806.3 linkuse as main transcript	c.854C>T	p.Ala285Val	missense_variant	3/5		XP_011515108.1
MFSD3	NR_130120.2 linkuse as main transcript	n.978C>T		non_coding_transcript_exon_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MFSD3	ENST00000301327.5 linkuse as main transcript	c.862C>T	p.Arg288Cys	missense_variant	3/5	1	NM_138431.3	ENSP00000301327	P1
MFSD3	ENST00000526749.1 linkuse as main transcript	n.667C>T		non_coding_transcript_exon_variant	2/2	2
MFSD3	ENST00000528047.5 linkuse as main transcript	n.968C>T		non_coding_transcript_exon_variant	2/3	3
MFSD3	ENST00000534427.1 linkuse as main transcript	n.384C>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000106

AC:

AN:

217358

Hom.:

AF XY:

0.0000859

AC XY:

AN XY:

116386

show subpopulations

Gnomad AFR exome

AF:

0.0000632

Gnomad AMR exome

AF:

0.000391

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000168

Gnomad SAS exome

AF:

0.0000862

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000505

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000537

AC:

AN:

1415784

Hom.:

Cov.:

AF XY:

0.0000415

AC XY:

AN XY:

698404

show subpopulations

Gnomad4 AFR exome

AF:

0.000185

Gnomad4 AMR exome

AF:

0.000244

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000179

Gnomad4 SAS exome

AF:

0.0000377

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000433

Gnomad4 OTH exome

AF:

0.0000514

GnomAD4 genome

AF:

0.0000919

AC:

AN:

152358

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000327

Hom.:

Bravo

AF:

0.0000945

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000907

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 12, 2024

The c.862C>T (p.R288C) alteration is located in exon 3 (coding exon 3) of the MFSD3 gene. This alteration results from a C to T substitution at nucleotide position 862, causing the arginine (R) at amino acid position 288 to be replaced by a cysteine (C). 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

0.092

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.47

CADD

Benign

1.3

DANN

Benign

0.96

DEOGEN2

Benign

0.061

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.72

M_CAP

Benign

0.071

MetaRNN

Benign

0.062

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

MutationTaster

Benign

1.0

PrimateAI

Benign

0.19

PROVEAN

Benign

-0.60

REVEL

Benign

0.13

Sift

Benign

0.19

Sift4G

Benign

0.089

Polyphen

0.85

Vest4

0.27

MVP

0.43

MPC

0.14

ClinPred

0.046

GERP RS

-1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.49

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over