Variant chr12-53253627-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000329548.5(MFSD5):c.792C>G(p.Phe264Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,613,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

MFSD5
ENST00000329548.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.46

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.31031513).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFSD5	NM_032889.5 linkuse as main transcript	c.792C>G	p.Phe264Leu	missense_variant	2/2	ENST00000329548.5	NP_116278.3	Q6N075-1
MFSD5	NM_001170790.2 linkuse as main transcript	c.1113C>G	p.Phe371Leu	missense_variant	2/2		NP_001164261.1	Q6N075-2
MFSD5	XM_005269197.2 linkuse as main transcript	c.1113C>G	p.Phe371Leu	missense_variant	3/3		XP_005269254.1	Q6N075-2
MFSD5	XM_005269198.5 linkuse as main transcript	c.792C>G	p.Phe264Leu	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.792C>G	p.Phe264Leu	missense_variant	2/2	1	NM_032889.5	ENSP00000332624.5	Q6N075-1
MFSD5	ENST00000534842.1 linkuse as main transcript	c.1113C>G	p.Phe371Leu	missense_variant	2/2	2		ENSP00000442688.1	Q6N075-2
MFSD5	ENST00000551660.2 linkuse as main transcript	c.1113C>G	p.Phe371Leu	missense_variant	2/2	2		ENSP00000449354.2	F8VV69

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152258

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:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251276

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135808

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:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461694

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727156

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:

0.000162

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74384

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:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000247

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

Dec 17, 2023

The c.1113C>G (p.F371L) alteration is located in exon 2 (coding exon 2) of the MFSD5 gene. This alteration results from a C to G substitution at nucleotide position 1113, causing the phenylalanine (F) at amino acid position 371 to be replaced by a leucine (L). 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

Pathogenic

0.77

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

.;T;T

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.79

T;T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.31

T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.95

.;.;L

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-3.7

D;D;D

REVEL

Uncertain

0.30

Sift

Uncertain

0.0080

D;T;T

Sift4G

Benign

0.23

T;T;T

Polyphen

0.010

.;.;B

Vest4

0.20

MutPred

0.68

.;.;Loss of sheet (P = 0.0228);

MVP

0.59

MPC

0.32

ClinPred

0.41

GERP RS

3.2

Varity_R

0.36

gMVP

0.69

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