NM_174983.5:c.298+2321T>C

Variant names:

• chr19-3554785-A-G
• rs1715093
• NM_174983.5:c.298+2321T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_174983.5(MFSD12):​c.298+2321T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 152,190 control chromosomes in the GnomAD database, including 20,395 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 0.51 (20395 hom., cov: 34)
• Consequence: MFSD12 NM_174983.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.384
• Publications: 9 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.82 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFSD12	NM_174983.5	MANE Select	c.298+2321T>C		intron	N/A	NP_778148.2
	MFSD12	NM_001287529.2		c.271+2348T>C		intron	N/A	NP_001274458.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFSD12	ENST00000355415.7	TSL:1 MANE Select	c.298+2321T>C		intron	N/A	ENSP00000347583.1
	MFSD12	ENST00000592652.1	TSL:5	c.128-6755T>C		intron	N/A	ENSP00000466906.1
	MFSD12	ENST00000585814.1	TSL:3	n.30-3591T>C		intron	N/A	ENSP00000465782.1

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77905 AN: 152072 Hom.: 20382 Cov.: 34

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.840

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.523

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

GnomAD4 genome AF: 0.512 AC: 77949 AN: 152190 Hom.: 20395 Cov.: 34 AF XY: 0.520 AC XY: 38669 AN XY: 74420

African (AFR) AF: 0.507 AC: 21069 AN: 41528

American (AMR) AF: 0.599 AC: 9157 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 1868 AN: 3472

East Asian (EAS) AF: 0.840 AC: 4348 AN: 5174

South Asian (SAS) AF: 0.573 AC: 2767 AN: 4826

European-Finnish (FIN) AF: 0.538 AC: 5697 AN: 10592

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.461 AC: 31373 AN: 67988

Other (OTH) AF: 0.527 AC: 1115 AN: 2116

Alfa AF: 0.483 Hom.: 9471

Bravo AF: 0.520

Asia WGS AF: 0.642 AC: 2229 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	2.5
DANN	Benign	0.46
PhyloP100		-0.38
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1715093; hg19: chr19-3554783;