Genetic Variant MFSD6:c.*1635T>G (chr2-190501853-T-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_017694.4(MFSD6):c.*1635T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 152,546 control chromosomes in the GnomAD database, including 5,068 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 0.23 ( 5046 hom., cov: 32)

Exomes 𝑓: 0.32 ( 22 hom. )

Consequence

MFSD6
NM_017694.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.55

Publications

17 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.32 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
MFSD6	NM_017694.4	MANE Select	c.*1635T>G	3_prime_UTR	Exon 8 of 8	NP_060164.3
MFSD6	NM_001375986.1		c.*1635T>G	3_prime_UTR	Exon 8 of 8	NP_001362915.1
MFSD6	NM_001375987.1		c.*1635T>G	3_prime_UTR	Exon 7 of 7	NP_001362916.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MFSD6	ENST00000392328.6	TSL:2 MANE Select	c.*1635T>G	3_prime_UTR	Exon 8 of 8	ENSP00000376141.1
MFSD6	ENST00000281416.11	TSL:1	c.*1635T>G	3_prime_UTR	Exon 6 of 6	ENSP00000281416.7
MFSD6	ENST00000434582.5	TSL:5	c.*1828T>G	3_prime_UTR	Exon 7 of 7	ENSP00000397276.1

Frequencies

GnomAD3 genomes

AF:

0.232

AC:

35230

AN:

151996

Hom.:

5045

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0851

Gnomad AMI

AF:

0.239

Gnomad AMR

AF:

0.176

Gnomad ASJ

AF:

0.176

Gnomad EAS

AF:

0.0790

Gnomad SAS

AF:

0.328

Gnomad FIN

AF:

0.348

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.324

Gnomad OTH

AF:

0.230

GnomAD4 exome

AF:

0.319

AC:

138

AN:

432

Hom.:

Cov.:

AF XY:

0.338

AC XY:

AN XY:

260

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.317

AC:

135

AN:

426

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.232

AC:

35217

AN:

152114

Hom.:

5046

Cov.:

AF XY:

0.231

AC XY:

17143

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.0849

AC:

3524

AN:

41510

American (AMR)

AF:

0.175

AC:

2680

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.176

AC:

612

AN:

3470

East Asian (EAS)

AF:

0.0783

AC:

406

AN:

5188

South Asian (SAS)

AF:

0.328

AC:

1584

AN:

4824

European-Finnish (FIN)

AF:

0.348

AC:

3670

AN:

10550

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.324

AC:

21993

AN:

67966

Other (OTH)

AF:

0.229

AC:

484

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1318

2637

3955

5274

6592

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

374

748

1122

1496

1870

<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:

0.259

Hom.:

8146

Bravo

AF:

0.206

Asia WGS

AF:

0.253

AC:

877

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.90

PhyloP100

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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