19-3546342-G-A

Variant names:

• chr19-3546342-G-A
• rs11555328
• NM_174983.5:c.1107C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_174983.5(MFSD12):​c.1107C>T​(p.Tyr369Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,606,754 control chromosomes in the GnomAD database, including 26,503 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3797 hom., cov: 34)
  • Exomes 𝑓: 0.17 (22706 hom.)
• Consequence: MFSD12 NM_174983.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.610
• Publications: 12 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 19-3546342-G-A is Benign according to our data. Variant chr19-3546342-G-A is described in ClinVar as Benign. ClinVar VariationId is 1236130.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.61 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.326 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFSD12	NM_174983.5	MANE Select	c.1107C>T	p.Tyr369Tyr	synonymous	Exon 7 of 10	NP_778148.2	Q6NUT3-1
	MFSD12	NM_001287529.2		c.1080C>T	p.Tyr360Tyr	synonymous	Exon 7 of 10	NP_001274458.1	Q6NUT3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFSD12	ENST00000355415.7	TSL:1 MANE Select	c.1107C>T	p.Tyr369Tyr	synonymous	Exon 7 of 10	ENSP00000347583.1	Q6NUT3-1
	MFSD12	ENST00000951867.1		c.1125C>T	p.Tyr375Tyr	synonymous	Exon 8 of 11	ENSP00000621926.1
	MFSD12	ENST00000589063.5	TSL:3	c.144C>T	p.Tyr48Tyr	synonymous	Exon 2 of 4	ENSP00000467635.1	K7EQ22

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31648 AN: 152160 Hom.: 3802 Cov.: 34

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.0129

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.197

GnomAD2 exomes AF: 0.168 AC: 38912 AN: 231856 AF XY: 0.169

Gnomad AFR exome AF: 0.342

Gnomad AMR exome AF: 0.131

Gnomad ASJ exome AF: 0.205

Gnomad EAS exome AF: 0.00938

Gnomad FIN exome AF: 0.175

Gnomad NFE exome AF: 0.172

Gnomad OTH exome AF: 0.167

GnomAD4 exome AF: 0.171 AC: 248979 AN: 1454476 Hom.: 22706 Cov.: 36 AF XY: 0.171 AC XY: 123360 AN XY: 723080

African (AFR) AF: 0.338 AC: 11313 AN: 33422

American (AMR) AF: 0.134 AC: 5861 AN: 43620

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 5287 AN: 25952

East Asian (EAS) AF: 0.0130 AC: 512 AN: 39428

South Asian (SAS) AF: 0.188 AC: 16037 AN: 85510

European-Finnish (FIN) AF: 0.173 AC: 8910 AN: 51406

Middle Eastern (MID) AF: 0.178 AC: 1023 AN: 5752

European-Non Finnish (NFE) AF: 0.171 AC: 189254 AN: 1109316

Other (OTH) AF: 0.179 AC: 10782 AN: 60070

GnomAD4 genome AF: 0.208 AC: 31660 AN: 152278 Hom.: 3797 Cov.: 34 AF XY: 0.203 AC XY: 15144 AN XY: 74460

African (AFR) AF: 0.331 AC: 13754 AN: 41560

American (AMR) AF: 0.146 AC: 2240 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 751 AN: 3472

East Asian (EAS) AF: 0.0127 AC: 66 AN: 5186

South Asian (SAS) AF: 0.172 AC: 832 AN: 4830

European-Finnish (FIN) AF: 0.172 AC: 1827 AN: 10620

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11508 AN: 67986

Other (OTH) AF: 0.200 AC: 423 AN: 2116

Alfa AF: 0.179 Hom.: 2184

Bravo AF: 0.212

Asia WGS AF: 0.134 AC: 463 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.069
DANN	Benign	0.79
PhyloP100		-0.61
PromoterAI		-0.12	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	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: rs11555328; hg19: chr19-3546340; COSMIC: COSV61536390; COSMIC: COSV61536390;