rs6493153

chr15-45481727-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013309.6(SLC30A4):c.*3436T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0845 in 152,180 control chromosomes in the GnomAD database, including 1,800 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 0.085 (1800 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC30A4 NM_013309.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.552

Genes affected

SLC30A4 (HGNC:11015): (solute carrier family 30 member 4) Zinc is the second most abundant trace metal in the human body. It is an essential element, serving both a structural role, as in the formation of zinc fingers in DNA-binding proteins, and a catalytic role in metalloenzymes, such as pancreatic carboxypeptidases (e.g., MIM 114852), alkaline phosphatases (e.g., MIM 171760), various dehydrogenases, and superoxide dismutases (e.g., MIM 147450). SLC30A4, or ZNT4, belongs to the ZNT family of zinc transporters. ZNTs are involved in transporting zinc out of the cytoplasm and have similar structures, consisting of 6 transmembrane domains and a histidine-rich cytoplasmic loop (Huang and Gitschier, 1997 [PubMed 9354792]).[supplied by OMIM, Mar 2008]

SLC30A4-AS1 (HGNC:56661): (SLC30A4 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC30A4	NM_013309.6	c.*3436T>G		3_prime_UTR_variant	8/8	ENST00000261867.5
SLC30A4	XM_017022560.3	c.*3436T>G		3_prime_UTR_variant	7/7
SLC30A4-AS1	XR_007064611.1	n.1913+5175A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC30A4	ENST00000261867.5	c.*3436T>G		3_prime_UTR_variant	8/8	1	NM_013309.6	P1
SLC30A4-AS1	ENST00000560647.5	n.555+5175A>C		intron_variant, non_coding_transcript_variant		3
SLC30A4-AS1	ENST00000558536.5	n.546+5175A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0844 AC: 12827 AN: 152062 Hom.: 1792 Cov.: 31

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0264

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.0227

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00141

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000970

Gnomad OTH AF: 0.0641

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0845 AC: 12863 AN: 152180 Hom.: 1800 Cov.: 31 AF XY: 0.0804 AC XY: 5985 AN XY: 74432

Gnomad4 AFR AF: 0.291

Gnomad4 AMR AF: 0.0264

Gnomad4 ASJ AF: 0.0127

Gnomad4 EAS AF: 0.0226

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00141

Gnomad4 NFE AF: 0.000956

Gnomad4 OTH AF: 0.0634

Alfa AF: 0.0171 Hom.: 517

Bravo AF: 0.0968

Asia WGS AF: 0.0330 AC: 115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.6
Dann	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs6493153; hg19: chr15-45773925;