Variant 12-53253241-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000329548.5(MFSD5):c.406C>T(p.Leu136Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000681 in 1,614,140 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

MFSD5
ENST00000329548.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.842

Variant links:

Genes affected

MFSD5 (HGNC:28156): (major facilitator superfamily domain containing 5) Predicted to enable molybdate ion transmembrane transporter activity. Predicted to be involved in molybdate ion transport. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

MFSD5 links:

MFSD5 (HGNC:):

MFSD5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
MFSD5	NM_032889.5 linkuse as main transcript	c.406C>T	p.Leu136Phe	missense_variant	2/2	ENST00000329548.5	NP_116278.3	Q6N075-1
MFSD5	NM_001170790.2 linkuse as main transcript	c.727C>T	p.Leu243Phe	missense_variant	2/2		NP_001164261.1	Q6N075-2
MFSD5	XM_005269197.2 linkuse as main transcript	c.727C>T	p.Leu243Phe	missense_variant	3/3		XP_005269254.1	Q6N075-2
MFSD5	XM_005269198.5 linkuse as main transcript	c.406C>T	p.Leu136Phe	missense_variant	2/2		XP_005269255.1	Q6N075-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MFSD5	ENST00000329548.5 linkuse as main transcript	c.406C>T	p.Leu136Phe	missense_variant	2/2	1	NM_032889.5	ENSP00000332624.5	Q6N075-1
MFSD5	ENST00000534842.1 linkuse as main transcript	c.727C>T	p.Leu243Phe	missense_variant	2/2	2		ENSP00000442688.1	Q6N075-2
MFSD5	ENST00000551660.2 linkuse as main transcript	c.727C>T	p.Leu243Phe	missense_variant	2/2	2		ENSP00000449354.2	F8VV69
MFSD5	ENST00000552097.1 linkuse as main transcript	n.*32C>T		downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251484

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

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

Nov 07, 2022

The c.727C>T (p.L243F) alteration is located in exon 2 (coding exon 2) of the MFSD5 gene. This alteration results from a C to T substitution at nucleotide position 727, causing the leucine (L) at amino acid position 243 to be replaced by a phenylalanine (F). 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

0.15

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.090

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

.;T;T

Eigen

Benign

0.075

Eigen_PC

Benign

-0.034

FATHMM_MKL

Benign

0.13

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Uncertain

0.095

MetaRNN

Uncertain

0.46

T;T;T

MetaSVM

Benign

-0.30

MutationAssessor

Uncertain

2.1

.;.;M

MutationTaster

Benign

0.96

N;N;N

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-2.4

N;N;N

REVEL

Uncertain

0.64

Sift

Benign

0.14

T;T;T

Sift4G

Uncertain

0.015

D;D;D

Polyphen

0.95

.;.;P

Vest4

0.84

MVP

0.74

MPC

0.87

ClinPred

0.56

GERP RS

3.3

Varity_R

0.17

gMVP

0.68

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