2-32193909-C-T

Variant names:

• chr2-32193909-C-T
• NM_017964.5:c.422C>T

Variant summary

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

The NM_017964.5(SLC30A6):​c.422C>T​(p.Thr141Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,460,956 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: 0.0000041 (0 hom.)
• Consequence: SLC30A6 NM_017964.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.36

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]

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 rank	MANE	Protein	UniProt
SLC30A6	NM_017964.5	c.422C>T	p.Thr141Ile	missense_variant	Exon 8 of 14	ENST00000282587.9	NP_060434.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC30A6	ENST00000282587.9	c.422C>T	p.Thr141Ile	missense_variant	Exon 8 of 14	1	NM_017964.5	ENSP00000282587.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1460956 Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4 AN XY: 726814

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: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.542C>T (p.T181I) 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 542, causing the threonine (T) at amino acid position 181 to be replaced by an isoleucine (I). 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	Pathogenic	0.83
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.20
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.077	.;.;T;.;T;T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.98	D;D;D;D;D;D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.73	D;D;D;D;D;D
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	1.3	.;L;.;.;L;.
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-2.3	.;N;D;N;N;N
REVEL	Uncertain	0.49
Sift	Uncertain	0.028	.;D;T;D;D;D
Sift4G	Uncertain	0.024	D;D;D;D;D;D
Polyphen		0.69, 0.93, 0.60	.;P;.;P;P;.
Vest4		0.77
MutPred		0.51		.;Loss of catalytic residue at T141 (P = 0.0265);.;.;Loss of catalytic residue at T141 (P = 0.0265);.;
MVP		0.59
MPC		0.15
ClinPred		0.93	D
GERP RS		5.7
Varity_R		0.30
gMVP		0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-32418978;