chr2-32193909-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017964.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC30A6	NM_017964.5	MANE Select	c.422C>T	p.Thr141Ile	missense	Exon 8 of 14	NP_060434.2
	SLC30A6	NM_001193513.3		c.542C>T	p.Thr181Ile	missense	Exon 9 of 15	NP_001180442.1	Q6NXT4-2
	SLC30A6	NM_001193514.3		c.422C>T	p.Thr141Ile	missense	Exon 8 of 13	NP_001180443.1	Q6NXT4-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC30A6	ENST00000282587.9	TSL:1 MANE Select	c.422C>T	p.Thr141Ile	missense	Exon 8 of 14	ENSP00000282587.5	Q6NXT4-1
	SLC30A6	ENST00000379343.6	TSL:1	c.542C>T	p.Thr181Ile	missense	Exon 9 of 15	ENSP00000368648.2	Q6NXT4-2
	SLC30A6	ENST00000435660.5	TSL:1	c.422C>T	p.Thr141Ile	missense	Exon 8 of 13	ENSP00000399005.1	Q6NXT4-3

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

African (AFR) AF: 0.00 AC: 0 AN: 33442

American (AMR) AF: 0.00 AC: 0 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39548

South Asian (SAS) AF: 0.00 AC: 0 AN: 86196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111530

Other (OTH) AF: 0.00 AC: 0 AN: 60328

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	1.3	L
PhyloP100		5.4
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.49
Sift	Uncertain	0.028	D
Sift4G	Uncertain	0.024	D
Polyphen		0.69	P
Vest4		0.77
MutPred		0.51		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
Mutation Taster		=37/63	disease causing

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

Other links and lift over

hg19: chr2-32418978;