Genetic Variant MFSD6L:p.Val514Met (chr17-8797581-C-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_152599.4(MFSD6L):c.1540G>A(p.Val514Met) variant causes a missense change. The variant allele was found at a frequency of 0.000112 in 1,613,450 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 0.00019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

MFSD6L
NM_152599.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.26

Publications

0 publications found

Variant links:

Genes affected

MFSD6L (HGNC:26656): (major facilitator superfamily domain containing 6 like) Predicted to be integral component of membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

MFSD6L Gene-Disease associations (from GenCC):

cataract
Inheritance: AR Classification: LIMITED Submitted by: G2P

MFSD6L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3436197).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152599.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFSD6L	NM_152599.4	MANE Select	c.1540G>A	p.Val514Met	missense	Exon 1 of 1	NP_689812.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFSD6L	ENST00000329805.6	TSL:6 MANE Select	c.1540G>A	p.Val514Met	missense	Exon 1 of 1	ENSP00000330051.4	Q8IWD5

Frequencies

GnomAD3 genomes

AF:

0.000191

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000168

AC:

AN:

250432

AF XY:

0.000148

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00210

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000104

AC:

152

AN:

1461130

Hom.:

Cov.:

AF XY:

0.0000963

AC XY:

AN XY:

726812

show subpopulations

African (AFR)

AF:

0.000329

AC:

AN:

33474

American (AMR)

AF:

0.0000447

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00161

AC:

AN:

26102

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86236

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53094

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000702

AC:

AN:

1111696

Other (OTH)

AF:

0.000232

AC:

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000190

AC:

AN:

152320

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.000409

AC:

AN:

41564

American (AMR)

AF:

0.000131

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000195

Hom.:

Bravo

AF:

0.000230

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000132

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000296

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.090

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0098

Eigen

Benign

0.17

Eigen_PC

Benign

0.022

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.80

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.34

MetaSVM

Uncertain

0.71

MutationAssessor

Uncertain

2.6

PhyloP100

4.3

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.54

REVEL

Uncertain

0.40

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.0050

Polyphen

1.0

Vest4

0.57

MVP

0.29

MPC

0.52

ClinPred

0.12

GERP RS

2.9

Varity_R

0.14

gMVP

0.44

Mutation Taster

=77/23

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over