Variant chr2-102718719-C-T 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.1126G>A(p.Ala376Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00312 in 1,613,890 control chromosomes in the GnomAD database, including 110 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.015 ( 62 hom., cov: 33)

Exomes 𝑓: 0.0018 ( 48 hom. )

Consequence

MFSD9
NM_032718.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.401

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=0.0029042363).

BP6

Variant 2-102718719-C-T is Benign according to our data. Variant chr2-102718719-C-T is described in ClinVar as [Benign]. Clinvar id is 775747.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0508 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.1126G>A	p.Ala376Thr	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.1126G>A	p.Ala376Thr	missense_variant	6/6	1	NM_032718.5	ENSP00000258436	P1
MFSD9	ENST00000437075.6 linkuse as main transcript	c.*927G>A		3_prime_UTR_variant, NMD_transcript_variant	7/7	5		ENSP00000414870
MFSD9	ENST00000438943.5 linkuse as main transcript	c.*962G>A		3_prime_UTR_variant, NMD_transcript_variant	7/7	5		ENSP00000408630

Frequencies

GnomAD3 genomes

AF:

0.0154

AC:

2346

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0528

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00523

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:

0.000441

Gnomad OTH

AF:

0.00956

GnomAD3 exomes

AF:

0.00442

AC:

1105

AN:

249732

Hom.:

AF XY:

0.00352

AC XY:

477

AN XY:

135344

show subpopulations

Gnomad AFR exome

AF:

0.0540

Gnomad AMR exome

AF:

0.00321

Gnomad ASJ exome

AF:

0.00627

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000356

Gnomad OTH exome

AF:

0.00376

GnomAD4 exome

AF:

0.00184

AC:

2691

AN:

1461564

Hom.:

Cov.:

AF XY:

0.00170

AC XY:

1236

AN XY:

727098

show subpopulations

Gnomad4 AFR exome

AF:

0.0533

Gnomad4 AMR exome

AF:

0.00382

Gnomad4 ASJ exome

AF:

0.00635

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000927

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000240

Gnomad4 OTH exome

AF:

0.00440

GnomAD4 genome

AF:

0.0154

AC:

2345

AN:

152326

Hom.:

Cov.:

AF XY:

0.0151

AC XY:

1125

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0527

Gnomad4 AMR

AF:

0.00523

Gnomad4 ASJ

AF:

0.00663

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000441

Gnomad4 OTH

AF:

0.00946

Alfa

AF:

0.00353

Hom.:

Bravo

AF:

0.0180

ESP6500AA

AF:

0.0531

AC:

234

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.00536

AC:

651

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000948

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.030

DANN

Benign

0.84

DEOGEN2

Benign

0.050

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.46

MetaRNN

Benign

0.0029

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

MutationTaster

Benign

1.0

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.47

REVEL

Benign

0.050

Sift

Benign

0.16

Sift4G

Benign

0.54

Polyphen

0.36

Vest4

0.023

MVP

0.12

MPC

0.040

ClinPred

0.0032

GERP RS

-5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.023

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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