Genetic Variant SLC30A6:p.Thr151Met (chr2-32193939-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001330477.2(SLC30A6):c.-166C>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.0000103 in 1,461,164 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

SLC30A6
NM_001330477.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.32

Variant links:

Genes affected

SLC30A6 (HGNC:19305): (solute carrier family 30 member 6) This gene encodes a member of a family of proteins that function as zinc transporters. This protein can regulate subcellular levels of zinc in the Golgi and vesicles. Expression of this gene is altered in the Alzheimer's disease brain plaques. [provided by RefSeq, Aug 2016]

SLC30A6 links:

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ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
SLC30A6	NM_017964.5 link	c.452C>T	p.Thr151Met	missense_variant	Exon 8 of 14	ENST00000282587.9	NP_060434.2	Q6NXT4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC30A6	ENST00000282587.9 link	c.452C>T	p.Thr151Met	missense_variant	Exon 8 of 14	1	NM_017964.5	ENSP00000282587.5		Q6NXT4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251106

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135728

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

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:

0.0000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1461164

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

726900

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000900

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.572C>T (p.T191M) alteration is located in exon 9 (coding exon 9) of the SLC30A6 gene. This alteration results from a C to T substitution at nucleotide position 572, causing the threonine (T) at amino acid position 191 to be replaced by a methionine (M). 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

0.23

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

0.12

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.035

.;.;T;.;T;T

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.97

D;D;D;D;D;D

M_CAP

Benign

0.030

MetaRNN

Uncertain

0.57

D;D;D;D;D;D

MetaSVM

Benign

-0.69

MutationAssessor

Benign

1.9

.;L;.;.;L;.

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.9

.;N;N;N;N;N

REVEL

Uncertain

0.30

Sift

Uncertain

0.012

.;D;D;T;T;T

Sift4G

Uncertain

0.022

D;D;D;D;D;D

Polyphen

0.96, 0.99, 0.69

.;D;.;D;P;.

Vest4

0.76

MutPred

0.57

.;Loss of helix (P = 0.2271);.;.;Loss of helix (P = 0.2271);.;

MVP

0.56

MPC

0.17

ClinPred

0.38

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.80

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over