2-32197799-G-T

Variant names:

• chr2-32197799-G-T
• NM_017964.5:c.638G>T

Variant summary

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

The NM_017964.5(SLC30A6):​c.638G>T​(p.Cys213Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC30A6 NM_017964.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.31

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.638G>T	p.Cys213Phe	missense_variant	Exon 10 of 14	ENST00000282587.9	NP_060434.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC30A6	ENST00000282587.9	c.638G>T	p.Cys213Phe	missense_variant	Exon 10 of 14	1	NM_017964.5	ENSP00000282587.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 16, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.758G>T (p.C253F) alteration is located in exon 11 (coding exon 11) of the SLC30A6 gene. This alteration results from a G to T substitution at nucleotide position 758, causing the cysteine (C) at amino acid position 253 to be replaced by a phenylalanine (F). 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	0.15
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.090
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.17	.;.;.;T;T
Eigen	Benign	0.0089
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D;D;D;D;D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.68	D;D;D;D;D
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.39	.;N;.;N;.
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-2.4	.;N;N;N;N
REVEL	Benign	0.26
Sift	Benign	0.24	.;T;T;T;T
Sift4G	Benign	0.34	T;T;T;T;T
Polyphen		0.029, 0.081, 0.036	.;B;B;B;.
Vest4		0.86
MutPred		0.44		.;Loss of catalytic residue at T215 (P = 0.1179);.;Loss of catalytic residue at T215 (P = 0.1179);.;
MVP		0.49
MPC		0.038
ClinPred		0.77	D
GERP RS		5.9
Varity_R		0.42
gMVP		0.90

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-32422868;