2-27257299-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003459.5(SLC30A3):c.632G>A(p.Gly211Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,636 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SLC30A3 NM_003459.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.03

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2319018).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC30A3	NM_003459.5	c.632G>A	p.Gly211Glu	missense_variant	5/8	ENST00000233535.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC30A3	ENST00000233535.9	c.632G>A	p.Gly211Glu	missense_variant	5/8	1	NM_003459.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461636 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727104

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

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

Apr 25, 2022

The c.632G>A (p.G211E) alteration is located in exon 5 (coding exon 5) of the SLC30A3 gene. This alteration results from a G to A substitution at nucleotide position 632, causing the glycine (G) at amino acid position 211 to be replaced by a glutamic acid (E). 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	Benign	0.11
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
Cadd	Benign	22
Dann	Benign	0.65
DEOGEN2	Benign	0.24	T;T;T
Eigen	Benign	0.024
Eigen_PC	Benign	0.080
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.80	T;T;T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	1.6	L;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.25
Sift	Benign	0.46	T;T;T
Sift4G	Benign	0.20	T;T;T
Polyphen		0.77	P;.;.
Vest4		0.67
MVP		0.65
MPC		0.74
ClinPred		0.30	T
GERP RS		5.2
Varity_R		0.18
gMVP		0.83

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: rs375191770; hg19: chr2-27480167; COSMIC: COSV51985458; COSMIC: COSV51985458;