rs1050631

Positions:

• chr18-36114157-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_012319.4(SLC39A6):​c.1783C>T​(p.Leu595Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 1,613,836 control chromosomes in the GnomAD database, including 89,289 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 0.30 (7259 hom., cov: 32)
  • Exomes 𝑓: 0.33 (82030 hom.)
• Consequence: SLC39A6 NM_012319.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37

Genes affected

SLC39A6 (HGNC:18607): (solute carrier family 39 member 6) Zinc is an essential cofactor for hundreds of enzymes. It is involved in protein, nucleic acid, carbohydrate, and lipid metabolism, as well as in the control of gene transcription, growth, development, and differentiation. SLC39A6 belongs to a subfamily of proteins that show structural characteristics of zinc transporters (Taylor and Nicholson, 2003 [PubMed 12659941]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP7: Synonymous conserved (PhyloP=1.37 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC39A6	NM_012319.4	c.1783C>T	p.Leu595Leu	synonymous_variant	7/10	ENST00000269187.10	NP_036451.4
SLC39A6	NM_001099406.2	c.958C>T	p.Leu320Leu	synonymous_variant	6/8		NP_001092876.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC39A6	ENST00000269187.10	c.1783C>T	p.Leu595Leu	synonymous_variant	7/10	2	NM_012319.4	ENSP00000269187.4
SLC39A6	ENST00000440549.6	c.958C>T	p.Leu320Leu	synonymous_variant	6/8	1		ENSP00000401139.1
SLC39A6	ENST00000590986.5	c.1783C>T	p.Leu595Leu	synonymous_variant	7/10	5		ENSP00000465915.1
SLC39A6	ENST00000586829.1	c.484C>T	p.Leu162Leu	synonymous_variant	3/5	3		ENSP00000467724.1

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45595 AN: 151974 Hom.: 7265 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.326

GnomAD3 exomes AF: 0.327 AC: 80882 AN: 247026 Hom.: 13794 AF XY: 0.326 AC XY: 43810 AN XY: 134232

Gnomad AFR exome AF: 0.202

Gnomad AMR exome AF: 0.396

Gnomad ASJ exome AF: 0.420

Gnomad EAS exome AF: 0.180

Gnomad SAS exome AF: 0.280

Gnomad FIN exome AF: 0.311

Gnomad NFE exome AF: 0.354

Gnomad OTH exome AF: 0.364

GnomAD4 exome AF: 0.332 AC: 484993 AN: 1461744 Hom.: 82030 Cov.: 43 AF XY: 0.331 AC XY: 240707 AN XY: 727176

Gnomad4 AFR exome AF: 0.206

Gnomad4 AMR exome AF: 0.391

Gnomad4 ASJ exome AF: 0.428

Gnomad4 EAS exome AF: 0.189

Gnomad4 SAS exome AF: 0.274

Gnomad4 FIN exome AF: 0.309

Gnomad4 NFE exome AF: 0.341

Gnomad4 OTH exome AF: 0.330

GnomAD4 genome AF: 0.300 AC: 45599 AN: 152092 Hom.: 7259 Cov.: 32 AF XY: 0.299 AC XY: 22224 AN XY: 74354

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.355

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.190

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.307

Gnomad4 NFE AF: 0.349

Gnomad4 OTH AF: 0.324

Alfa AF: 0.348 Hom.: 21759

Bravo AF: 0.302

Asia WGS AF: 0.252 AC: 879 AN: 3478

EpiCase AF: 0.366

EpiControl AF: 0.371

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.3
DANN	Benign	0.63

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

Other links and lift over

dbSNP: rs1050631; hg19: chr18-33694120; COSMIC: COSV52368396;