dbSNP rs4129081: MFSD6:c.1532+5121G>T (chr2-190442682-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.1532+5121G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 151,850 control chromosomes in the GnomAD database, including 9,175 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 0.33 ( 9175 hom., cov: 31)

Exomes 𝑓: 0.20 ( 0 hom. )

Consequence

MFSD6
NM_017694.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.106

Publications

12 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:

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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=-0.85).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.465 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.1532+5121G>T	intron	N/A	NP_060164.3
MFSD6	NM_001375986.1		c.1532+5121G>T	intron	N/A	NP_001362915.1	Q6ZSS7
MFSD6	NM_001375987.1		c.1532+5121G>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.1532+5121G>T	intron	N/A	ENSP00000376141.1	Q6ZSS7
MFSD6	ENST00000281416.11	TSL:1	c.1532+5121G>T	intron	N/A	ENSP00000281416.7	Q6ZSS7
MFSD6	ENST00000861426.1		c.1532+5121G>T	intron	N/A	ENSP00000531485.1

Frequencies

GnomAD3 genomes

AF:

0.332

AC:

50427

AN:

151722

Hom.:

9148

Cov.:

show subpopulations

Gnomad AFR

AF:

0.390

Gnomad AMI

AF:

0.223

Gnomad AMR

AF:

0.473

Gnomad ASJ

AF:

0.295

Gnomad EAS

AF:

0.458

Gnomad SAS

AF:

0.227

Gnomad FIN

AF:

0.427

Gnomad MID

AF:

0.239

Gnomad NFE

AF:

0.254

Gnomad OTH

AF:

0.308

GnomAD4 exome

AF:

0.200

AC:

AN:

Hom.:

Cov.:

AF XY:

0.167

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.125

AC:

AN:

Other (OTH)

AC:

AN:

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

GnomAD4 genome

AF:

0.333

AC:

50498

AN:

151840

Hom.:

9175

Cov.:

AF XY:

0.343

AC XY:

25466

AN XY:

74198

show subpopulations

African (AFR)

AF:

0.390

AC:

16147

AN:

41374

American (AMR)

AF:

0.474

AC:

7238

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.295

AC:

1023

AN:

3466

East Asian (EAS)

AF:

0.458

AC:

2361

AN:

5154

South Asian (SAS)

AF:

0.227

AC:

1092

AN:

4810

European-Finnish (FIN)

AF:

0.427

AC:

4485

AN:

10514

Middle Eastern (MID)

AF:

0.247

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.254

AC:

17227

AN:

67940

Other (OTH)

AF:

0.308

AC:

650

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1609

3217

4826

6434

8043

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

484

968

1452

1936

2420

<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:

0.277

Hom.:

10677

Bravo

AF:

0.346

Asia WGS

AF:

0.331

AC:

1155

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.1

(source)

DANN

Benign

0.61

PhyloP100

0.11

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

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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