Genetic Variant MFSD12:p.Thr122Thr (chr19-3551127-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_174983.5(MFSD12):c.366G>A(p.Thr122Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00625 in 1,612,918 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0056 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0063 ( 35 hom. )

Consequence

MFSD12
NM_174983.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.86

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:

ENSG00000267436 (HGNC:56727): (MFSD12 antisense RNA 1)

ENSG00000267436 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 19-3551127-C-T is Benign according to our data. Variant chr19-3551127-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2648994.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MFSD12	NM_174983.5 link	c.366G>A	p.Thr122Thr	synonymous_variant	Exon 2 of 10	ENST00000355415.7	NP_778148.2	Q6NUT3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MFSD12	ENST00000355415.7 link	c.366G>A	p.Thr122Thr	synonymous_variant	Exon 2 of 10	1	NM_174983.5	ENSP00000347583.1		Q6NUT3-1

Frequencies

GnomAD3 genomes

AF:

0.00558

AC:

849

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.0176

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00809

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00963

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00597

AC:

1474

AN:

246864

Hom.:

AF XY:

0.00596

AC XY:

803

AN XY:

134662

show subpopulations

Gnomad AFR exome

AF:

0.000920

Gnomad AMR exome

AF:

0.00195

Gnomad ASJ exome

AF:

0.00422

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000916

Gnomad FIN exome

AF:

0.00988

Gnomad NFE exome

AF:

0.00976

Gnomad OTH exome

AF:

0.00401

GnomAD4 exome

AF:

0.00632

AC:

9231

AN:

1460588

Hom.:

Cov.:

AF XY:

0.00637

AC XY:

4631

AN XY:

726610

show subpopulations

Gnomad4 AFR exome

AF:

0.000777

Gnomad4 AMR exome

AF:

0.00186

Gnomad4 ASJ exome

AF:

0.00410

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00103

Gnomad4 FIN exome

AF:

0.00918

Gnomad4 NFE exome

AF:

0.00732

Gnomad4 OTH exome

AF:

0.00497

GnomAD4 genome

AF:

0.00557

AC:

848

AN:

152330

Hom.:

Cov.:

AF XY:

0.00503

AC XY:

375

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00115

Gnomad4 AMR

AF:

0.00163

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00809

Gnomad4 NFE

AF:

0.00963

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00704

Hom.:

Bravo

AF:

0.00473

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00682

EpiControl

AF:

0.00765

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Oct 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MFSD12: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.69

DANN

Benign

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over