dbSNP rs3811608: MFSD6:c.1630+476T>C (chr2-190470331-T-C) – 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.1630+476T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,234 control chromosomes in the GnomAD database, including 1,849 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 0.15 ( 1849 hom., cov: 32)

Consequence

MFSD6
NM_017694.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.620

Publications

1 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=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.186 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.1630+476T>C	intron	N/A	NP_060164.3
MFSD6	NM_001375986.1		c.1630+476T>C	intron	N/A	NP_001362915.1	Q6ZSS7
MFSD6	NM_001375987.1		c.1630+476T>C	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.1630+476T>C	intron	N/A	ENSP00000376141.1	Q6ZSS7
MFSD6	ENST00000281416.11	TSL:1	c.1630+476T>C	intron	N/A	ENSP00000281416.7	Q6ZSS7
MFSD6	ENST00000861426.1		c.1630+476T>C	intron	N/A	ENSP00000531485.1

Frequencies

GnomAD3 genomes

AF:

0.147

AC:

22297

AN:

152116

Hom.:

1848

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0758

Gnomad AMI

AF:

0.184

Gnomad AMR

AF:

0.141

Gnomad ASJ

AF:

0.246

Gnomad EAS

AF:

0.148

Gnomad SAS

AF:

0.161

Gnomad FIN

AF:

0.115

Gnomad MID

AF:

0.217

Gnomad NFE

AF:

0.188

Gnomad OTH

AF:

0.163

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

GnomAD4 genome

AF:

0.146

AC:

22299

AN:

152234

Hom.:

1849

Cov.:

AF XY:

0.144

AC XY:

10692

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.0758

AC:

3149

AN:

41562

American (AMR)

AF:

0.141

AC:

2155

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.246

AC:

853

AN:

3470

East Asian (EAS)

AF:

0.148

AC:

767

AN:

5178

South Asian (SAS)

AF:

0.161

AC:

778

AN:

4818

European-Finnish (FIN)

AF:

0.115

AC:

1218

AN:

10586

Middle Eastern (MID)

AF:

0.219

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.188

AC:

12807

AN:

68000

Other (OTH)

AF:

0.161

AC:

340

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

960

1920

2879

3839

4799

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

250

500

750

1000

1250

<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:

0.157

Hom.:

288

Bravo

AF:

0.144

Asia WGS

AF:

0.122

AC:

424

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.4

(source)

DANN

Benign

0.59

PhyloP100

0.62

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