Genetic Variant MFSD6:p.Asn66Lys (chr2-190436227-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017694.4(MFSD6):c.198C>G(p.Asn66Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N66N) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

MFSD6
NM_017694.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.02

Publications

3 publications found

Variant links:

Genes affected

MFSD6 (HGNC:24711): (major facilitator superfamily domain containing 6) Predicted to enable MHC class I protein binding activity and MHC class I receptor activity. Predicted to be involved in antigen processing and presentation of exogenous peptide antigen via MHC class I. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

MFSD6 links:

NEMP2 (HGNC:33700): (nuclear envelope integral membrane protein 2) Predicted to be located in nuclear inner membrane. Predicted to be integral component of membrane. Predicted to be active in nuclear envelope. [provided by Alliance of Genome Resources, Apr 2022]

NEMP2 links:

ENSG00000309564 (HGNC:):

ENSG00000309564 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08243975).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017694.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MFSD6	NM_017694.4	MANE Select	c.198C>G	p.Asn66Lys	missense	Exon 3 of 8	NP_060164.3
MFSD6	NM_001375986.1		c.198C>G	p.Asn66Lys	missense	Exon 3 of 8	NP_001362915.1	Q6ZSS7
MFSD6	NM_001375987.1		c.198C>G	p.Asn66Lys	missense	Exon 2 of 7	NP_001362916.1	Q6ZSS7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MFSD6	ENST00000392328.6	TSL:2 MANE Select	c.198C>G	p.Asn66Lys	missense	Exon 3 of 8	ENSP00000376141.1	Q6ZSS7
MFSD6	ENST00000281416.11	TSL:1	c.198C>G	p.Asn66Lys	missense	Exon 1 of 6	ENSP00000281416.7	Q6ZSS7
MFSD6	ENST00000861426.1		c.198C>G	p.Asn66Lys	missense	Exon 2 of 7	ENSP00000531485.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000797

AC:

AN:

251098

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461710

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727184

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33446

American (AMR)

AF:

0.00

AC:

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000696

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111922

Other (OTH)

AF:

0.00

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.065

(source)

DANN

Benign

0.54

DEOGEN2

Benign

0.0033

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.25

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.0092

MetaRNN

Benign

0.082

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

-1.0

PrimateAI

Uncertain

0.61

PROVEAN

Benign

0.17

REVEL

Benign

0.16

Sift

Benign

0.91

Sift4G

Benign

0.26

Polyphen

0.87

Vest4

0.53

MutPred

0.56

Gain of methylation at N66 (P = 0.0077)

MVP

0.076

MPC

0.52

ClinPred

0.11

GERP RS

-3.7

PromoterAI

0.010

Neutral

(source)

Varity_R

0.057

gMVP

0.23

Mutation Taster

=88/12

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over