2-27258239-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003459.5(SLC30A3):c.346A>T(p.Met116Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000836 in 1,434,620 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000084 (0 hom.)
• Consequence: SLC30A3 NM_003459.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.91

Genes affected

SLC30A3 (HGNC:11014): (solute carrier family 30 member 3) Predicted to enable zinc ion transmembrane transporter activity. Involved in regulation of sequestering of zinc ion. Located in late endosome and synaptic vesicle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC30A3	NM_003459.5	c.346A>T	p.Met116Leu	missense_variant	3/8	ENST00000233535.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC30A3	ENST00000233535.9	c.346A>T	p.Met116Leu	missense_variant	3/8	1	NM_003459.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000866 AC: 2 AN: 230958 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 123896

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000191

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000836 AC: 12 AN: 1434620 Hom.: 0 Cov.: 31 AF XY: 0.00000704 AC XY: 5 AN XY: 710100

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000912

Gnomad4 OTH exome AF: 0.0000338

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 24, 2022

The c.346A>T (p.M116L) alteration is located in exon 3 (coding exon 3) of the SLC30A3 gene. This alteration results from a A to T substitution at nucleotide position 346, causing the methionine (M) at amino acid position 116 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
Cadd	Uncertain	24
Dann	Benign	0.97
DEOGEN2	Benign	0.22	T;T;T;.;.;.
Eigen	Benign	0.078
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.96	D;D;D;D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.45	T;T;T;T;T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	-0.36	N;.;.;.;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.3	N;N;N;N;N;N
REVEL	Benign	0.26
Sift	Benign	0.059	T;T;T;T;D;D
Sift4G	Benign	0.13	T;T;T;.;.;.
Polyphen		0.60	P;.;.;.;.;.
Vest4		0.61
MutPred		0.77		Gain of glycosylation at S115 (P = 0.1144);.;.;.;.;.;
MVP		0.53
MPC		0.70
ClinPred		0.40	T
GERP RS		5.5
Varity_R		0.32
gMVP		0.73

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

Other links and lift over

dbSNP: rs756363639; hg19: chr2-27481107;