Variant 2-102718524-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032718.5(MFSD9):c.1321C>G(p.Pro441Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00348 in 1,613,532 control chromosomes in the GnomAD database, including 125 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 68 hom., cov: 33)

Exomes 𝑓: 0.0021 ( 57 hom. )

Consequence

MFSD9
NM_032718.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 9.30

Variant links:

Genes affected

MFSD9 (HGNC:28158): (major facilitator superfamily domain containing 9) Predicted to enable transmembrane transporter activity. Predicted to be involved in transmembrane transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

MFSD9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0088353455).

BP6

Variant 2-102718524-G-C is Benign according to our data. Variant chr2-102718524-G-C is described in ClinVar as [Benign]. Clinvar id is 775746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFSD9	NM_032718.5 linkuse as main transcript	c.1321C>G	p.Pro441Ala	missense_variant	6/6	ENST00000258436.10	NP_116107.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MFSD9	ENST00000258436.10 linkuse as main transcript	c.1321C>G	p.Pro441Ala	missense_variant	6/6	1	NM_032718.5	ENSP00000258436	P1
MFSD9	ENST00000437075.6 linkuse as main transcript	c.*1122C>G		3_prime_UTR_variant, NMD_transcript_variant	7/7	5		ENSP00000414870
MFSD9	ENST00000438943.5 linkuse as main transcript	c.*1157C>G		3_prime_UTR_variant, NMD_transcript_variant	7/7	5		ENSP00000408630

Frequencies

GnomAD3 genomes

AF:

0.0169

AC:

2569

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0573

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00661

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000632

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.00491

AC:

1220

AN:

248506

Hom.:

AF XY:

0.00391

AC XY:

527

AN XY:

134814

show subpopulations

Gnomad AFR exome

AF:

0.0594

Gnomad AMR exome

AF:

0.00359

Gnomad ASJ exome

AF:

0.00647

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000562

Gnomad OTH exome

AF:

0.00417

GnomAD4 exome

AF:

0.00209

AC:

3052

AN:

1461254

Hom.:

Cov.:

AF XY:

0.00194

AC XY:

1410

AN XY:

726924

show subpopulations

Gnomad4 AFR exome

AF:

0.0585

Gnomad4 AMR exome

AF:

0.00432

Gnomad4 ASJ exome

AF:

0.00637

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000354

Gnomad4 OTH exome

AF:

0.00500

GnomAD4 genome

AF:

0.0169

AC:

2570

AN:

152278

Hom.:

Cov.:

AF XY:

0.0165

AC XY:

1226

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0572

Gnomad4 AMR

AF:

0.00660

Gnomad4 ASJ

AF:

0.00663

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000632

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.00234

Hom.:

Bravo

AF:

0.0198

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0572

AC:

252

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.00592

AC:

719

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.00113

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 11, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.047

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.91

MetaRNN

Benign

0.0088

MetaSVM

Benign

-0.44

MutationAssessor

Uncertain

2.9

MutationTaster

Benign

1.0

PrimateAI

Benign

0.48

PROVEAN

Pathogenic

-4.5

REVEL

Uncertain

0.59

Sift

Uncertain

0.026

Sift4G

Benign

0.10

Polyphen

1.0

Vest4

0.61

MVP

0.85

MPC

0.25

ClinPred

0.067

GERP RS

4.6

Varity_R

0.28

gMVP

0.63

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