Variant 3-158819658-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 NM_022736.4(MFSD1):c.662C>T(p.Thr221Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000217 in 1,520,268 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000087 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

MFSD1
NM_022736.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.83

Variant links:

Genes affected

MFSD1 (HGNC:25874): (major facilitator superfamily domain containing 1) Predicted to enable protein homodimerization activity. Predicted to be involved in protein localization to lysosome and protein stabilization. Predicted to be located in lysosome. [provided by Alliance of Genome Resources, Apr 2022]

MFSD1 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
MFSD1	NM_022736.4 linkuse as main transcript	c.662C>T	p.Thr221Met	missense_variant	8/16	ENST00000415822.8	NP_073573.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFSD1	ENST00000415822.8 linkuse as main transcript	c.662C>T	p.Thr221Met	missense_variant	8/16	1	NM_022736.4	ENSP00000403117	P2	Q9H3U5-1

Frequencies

GnomAD3 genomes

AF:

0.0000804

AC:

AN:

149294

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000247

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:

0.0000296

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000171

AC:

AN:

234410

Hom.:

AF XY:

0.00000786

AC XY:

AN XY:

127286

show subpopulations

Gnomad AFR exome

AF:

0.000132

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:

0.00

Gnomad OTH exome

AF:

0.000357

GnomAD4 exome

AF:

0.0000146

AC:

AN:

1370874

Hom.:

Cov.:

AF XY:

0.0000131

AC XY:

AN XY:

685878

show subpopulations

Gnomad4 AFR exome

AF:

0.000292

Gnomad4 AMR exome

AF:

0.0000241

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000245

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000674

Gnomad4 OTH exome

AF:

0.0000176

GnomAD4 genome

AF:

0.0000870

AC:

AN:

149394

Hom.:

Cov.:

AF XY:

0.0000689

AC XY:

AN XY:

72620

show subpopulations

Gnomad4 AFR

AF:

0.000271

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:

0.0000296

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.000125

ExAC

AF:

0.00000824

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

Mar 17, 2023

The c.809C>T (p.T270M) alteration is located in exon 8 (coding exon 8) of the MFSD1 gene. This alteration results from a C to T substitution at nucleotide position 809, causing the threonine (T) at amino acid position 270 to be replaced by a methionine (M). 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

0.20

BayesDel_addAF

Uncertain

0.075

BayesDel_noAF

Uncertain

0.12

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

.;.;.;T;.

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

.;D;D;D;D

M_CAP

Uncertain

0.089

MetaRNN

Uncertain

0.68

D;D;D;D;D

MetaSVM

Uncertain

0.015

MutationAssessor

Uncertain

2.3

.;.;.;M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.1

D;.;D;D;D

REVEL

Uncertain

0.33

Sift

Benign

0.031

D;.;D;D;D

Sift4G

Uncertain

0.051

T;T;D;T;T

Polyphen

0.97

.;.;.;D;.

Vest4

0.84

MVP

0.94

MPC

0.26

ClinPred

0.81

GERP RS

5.6

Varity_R

0.17

gMVP

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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