Genetic Variant MFSD6:c.1631-6073G>T (chr2-190482584-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_017694.4(MFSD6):c.1631-6073G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 151,770 control chromosomes in the GnomAD database, including 7,492 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.30 ( 7492 hom., cov: 30)

Consequence

MFSD6
NM_017694.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00100

Publications

8 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

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	Effect	Exon Rank	Protein	UniProt
MFSD6	NM_017694.4	MANE Select	c.1631-6073G>T	intron	N/A	NP_060164.3
MFSD6	NM_001375986.1		c.1631-6073G>T	intron	N/A	NP_001362915.1	Q6ZSS7
MFSD6	NM_001375987.1		c.1631-6073G>T	intron	N/A	NP_001362916.1	Q6ZSS7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MFSD6	ENST00000392328.6	TSL:2 MANE Select	c.1631-6073G>T	intron	N/A	ENSP00000376141.1	Q6ZSS7
MFSD6	ENST00000281416.11	TSL:1	c.1631-6073G>T	intron	N/A	ENSP00000281416.7	Q6ZSS7
MFSD6	ENST00000861426.1		c.1631-6073G>T	intron	N/A	ENSP00000531485.1

Frequencies

GnomAD3 genomes

AF:

0.298

AC:

45234

AN:

151652

Hom.:

7479

Cov.:

show subpopulations

Gnomad AFR

AF:

0.270

Gnomad AMI

AF:

0.226

Gnomad AMR

AF:

0.458

Gnomad ASJ

AF:

0.293

Gnomad EAS

AF:

0.464

Gnomad SAS

AF:

0.221

Gnomad FIN

AF:

0.427

Gnomad MID

AF:

0.236

Gnomad NFE

AF:

0.255

Gnomad OTH

AF:

0.279

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.298

AC:

45275

AN:

151770

Hom.:

7492

Cov.:

AF XY:

0.311

AC XY:

23030

AN XY:

74160

show subpopulations

African (AFR)

AF:

0.270

AC:

11162

AN:

41360

American (AMR)

AF:

0.459

AC:

7013

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.293

AC:

1017

AN:

3468

East Asian (EAS)

AF:

0.463

AC:

2381

AN:

5140

South Asian (SAS)

AF:

0.221

AC:

1061

AN:

4808

European-Finnish (FIN)

AF:

0.427

AC:

4470

AN:

10480

Middle Eastern (MID)

AF:

0.243

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.255

AC:

17305

AN:

67930

Other (OTH)

AF:

0.280

AC:

590

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1505

3010

4516

6021

7526

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

450

900

1350

1800

2250

<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:

0.309

Hom.:

1412

Bravo

AF:

0.308

Asia WGS

AF:

0.329

AC:

1150

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

3.4

(source)

DANN

Benign

0.70

PhyloP100

0.0010

Mutation Taster

=100/0

polymorphism (auto)

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over