Genetic Variant MFSD12:p.Gly395Ser (chr19-3546266-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_174983.5(MFSD12):c.1183G>A(p.Gly395Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00821 in 1,610,588 control chromosomes in the GnomAD database, including 86 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0047 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0086 ( 81 hom. )

Consequence

MFSD12
NM_174983.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.27

Publications

7 publications found

Variant links:

Genes affected

MFSD12 (HGNC:28299): (major facilitator superfamily domain containing 12) Enables cysteine transmembrane transporter activity. Involved in cysteine transmembrane transport; pigment metabolic process involved in pigmentation; and regulation of melanin biosynthetic process. Located in lysosome and melanosome. Part of late endosome. [provided by Alliance of Genome Resources, Apr 2022]

MFSD12 links:

MFSD12-AS1 (HGNC:56727): (MFSD12 antisense RNA 1)

MFSD12-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015567243).

BP6

Variant 19-3546266-C-T is Benign according to our data. Variant chr19-3546266-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2648992.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174983.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFSD12	NM_174983.5	MANE Select	c.1183G>A	p.Gly395Ser	missense	Exon 7 of 10	NP_778148.2	Q6NUT3-1
	MFSD12	NM_001287529.2		c.1156G>A	p.Gly386Ser	missense	Exon 7 of 10	NP_001274458.1	Q6NUT3-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MFSD12	ENST00000355415.7	TSL:1 MANE Select	c.1183G>A	p.Gly395Ser	missense	Exon 7 of 10	ENSP00000347583.1	Q6NUT3-1
MFSD12	ENST00000951867.1		c.1201G>A	p.Gly401Ser	missense	Exon 8 of 11	ENSP00000621926.1
MFSD12	ENST00000589063.5	TSL:3	c.220G>A	p.Gly74Ser	missense	Exon 2 of 4	ENSP00000467635.1	K7EQ22

Frequencies

GnomAD3 genomes

AF:

0.00474

AC:

721

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00181

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00883

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00356

AC:

856

AN:

240426

AF XY:

0.00354

show subpopulations

Gnomad AFR exome

AF:

0.00149

Gnomad AMR exome

AF:

0.00104

Gnomad ASJ exome

AF:

0.000919

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000690

Gnomad NFE exome

AF:

0.00691

Gnomad OTH exome

AF:

0.00428

GnomAD4 exome

AF:

0.00858

AC:

12505

AN:

1458274

Hom.:

Cov.:

AF XY:

0.00817

AC XY:

5925

AN XY:

725322

show subpopulations

African (AFR)

AF:

0.00126

AC:

AN:

33456

American (AMR)

AF:

0.00127

AC:

AN:

44262

Ashkenazi Jewish (ASJ)

AF:

0.00108

AC:

AN:

26040

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39590

South Asian (SAS)

AF:

0.000105

AC:

AN:

85992

European-Finnish (FIN)

AF:

0.000578

AC:

AN:

51910

Middle Eastern (MID)

AF:

0.000521

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0107

AC:

11932

AN:

1111002

Other (OTH)

AF:

0.00670

AC:

404

AN:

60260

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

791

1581

2372

3162

3953

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

486

972

1458

1944

2430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00474

AC:

722

AN:

152314

Hom.:

Cov.:

AF XY:

0.00416

AC XY:

310

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.00180

AC:

AN:

41562

American (AMR)

AF:

0.00189

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.000471

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00885

AC:

602

AN:

68036

Other (OTH)

AF:

0.00331

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

102

136

170

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00508

Hom.:

Bravo

AF:

0.00459

TwinsUK

AF:

0.00890

AC:

ALSPAC

AF:

0.00856

AC:

ESP6500AA

AF:

0.00140

AC:

ESP6500EA

AF:

0.00684

AC:

ExAC

AF:

0.00331

AC:

400

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Uncertain

-0.060

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.54

Eigen

Pathogenic

0.70

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.95

M_CAP

Pathogenic

0.30

MetaRNN

Benign

0.016

MetaSVM

Uncertain

0.52

MutationAssessor

Benign

2.0

PhyloP100

7.3

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-4.9

REVEL

Uncertain

0.60

Sift

Benign

0.050

Sift4G

Uncertain

0.029

Polyphen

0.99

Vest4

0.61

MVP

0.74

ClinPred

0.026

GERP RS

4.6

PromoterAI

-0.025

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.59

gMVP

0.84

Mutation Taster

=96/4

polymorphism

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over