Variant 3-158802076-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 ENST00000622669.4(MFSD1):c.71C>T(p.Thr24Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000526 in 1,567,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00056 ( 0 hom. )

Consequence

MFSD1
ENST00000622669.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.574

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 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=0.026380599).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MFSD1	NM_022736.4 linkuse as main transcript	c.-77C>T		5_prime_UTR_variant	1/16	ENST00000415822.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MFSD1	ENST00000415822.8 linkuse as main transcript	c.-77C>T		5_prime_UTR_variant	1/16	1	NM_022736.4	P2	Q9H3U5-1

Frequencies

GnomAD3 genomes

AF:

0.000184

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

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:

0.000338

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000168

AC:

AN:

178246

Hom.:

AF XY:

0.000208

AC XY:

AN XY:

96368

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000362

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:

0.000336

Gnomad OTH exome

AF:

0.000628

GnomAD4 exome

AF:

0.000562

AC:

796

AN:

1415560

Hom.:

Cov.:

AF XY:

0.000507

AC XY:

355

AN XY:

700692

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000259

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000717

Gnomad4 OTH exome

AF:

0.000187

GnomAD4 genome

AF:

0.000184

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.000121

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:

0.000338

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.000189

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.000133

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

Jan 06, 2023

The c.71C>T (p.T24I) alteration is located in exon 1 (coding exon 1) of the MFSD1 gene. This alteration results from a C to T substitution at nucleotide position 71, causing the threonine (T) at amino acid position 24 to be replaced by an isoleucine (I). 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

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.83

Cadd

Benign

4.3

Dann

Benign

0.75

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.25

M_CAP

Benign

0.0035

MetaRNN

Benign

0.026

T;T;T

MetaSVM

Benign

-0.96

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.020

N;.;N

REVEL

Benign

0.012

Sift

Benign

0.67

T;.;T

Sift4G

Pathogenic

0.0

D;D;.

Vest4

0.077

MVP

0.10

MPC

0.20

ClinPred

0.0096

GERP RS

-0.19

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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