Genetic Variant MFSD12:c.1290-85G>A (chr19-3545024-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_174983.5(MFSD12):c.1290-85G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0206 in 1,490,504 control chromosomes in the GnomAD database, including 1,964 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.069 ( 1068 hom., cov: 32)

Exomes 𝑓: 0.015 ( 896 hom. )

Consequence

MFSD12
NM_174983.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.506

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 19-3545024-C-T is Benign according to our data. Variant chr19-3545024-C-T is described in ClinVar as [Benign]. Clinvar id is 492942.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MFSD12	NM_174983.5 link	c.1290-85G>A		intron_variant	Intron 8 of 9	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.1290-85G>A		intron_variant	Intron 8 of 9	1	NM_174983.5	ENSP00000347583.1		Q6NUT3-1

Frequencies

GnomAD3 genomes

AF:

0.0694

AC:

10541

AN:

151974

Hom.:

1062

Cov.:

show subpopulations

Gnomad AFR

AF:

0.220

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0294

Gnomad ASJ

AF:

0.0332

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00950

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0101

Gnomad OTH

AF:

0.0488

GnomAD4 exome

AF:

0.0151

AC:

20185

AN:

1338412

Hom.:

896

AF XY:

0.0141

AC XY:

9205

AN XY:

655148

show subpopulations

Gnomad4 AFR exome

AF:

0.226

Gnomad4 AMR exome

AF:

0.0181

Gnomad4 ASJ exome

AF:

0.0325

Gnomad4 EAS exome

AF:

0.00232

Gnomad4 SAS exome

AF:

0.00170

Gnomad4 FIN exome

AF:

0.00682

Gnomad4 NFE exome

AF:

0.00961

Gnomad4 OTH exome

AF:

0.0225

GnomAD4 genome

AF:

0.0695

AC:

10567

AN:

152092

Hom.:

1068

Cov.:

AF XY:

0.0673

AC XY:

5003

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.220

Gnomad4 AMR

AF:

0.0294

Gnomad4 ASJ

AF:

0.0332

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00950

Gnomad4 NFE

AF:

0.0101

Gnomad4 OTH

AF:

0.0483

Alfa

AF:

0.0111

Hom.:

Bravo

AF:

0.0783

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 29025994) -

MFSD12 POLYMORPHISM

Benign:1

Feb 03, 2020

OMIM

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.49

DANN

Benign

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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