chr2-32171341-C-T

Variant names:

• chr2-32171341-C-T
• rs764733512
• NM_017964.5:c.58C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001330479.2(SLC30A6):​c.-90C>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.000018 in 1,613,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: SLC30A6 NM_001330479.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.29
• Publications: 2 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_001330479.2. 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.58C>T	p.Arg20Trp	missense	Exon 2 of 14	NP_060434.2
	SLC30A6	NM_001330479.2		c.-90C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 14	NP_001317408.1
	SLC30A6	NM_001330477.2		c.-517C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 13	NP_001317406.1	B3KU87

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC30A6	ENST00000282587.9	TSL:1 MANE Select	c.58C>T	p.Arg20Trp	missense	Exon 2 of 14	ENSP00000282587.5	Q6NXT4-1
	SLC30A6	ENST00000379343.6	TSL:1	c.58C>T	p.Arg20Trp	missense	Exon 2 of 15	ENSP00000368648.2	Q6NXT4-2
	SLC30A6	ENST00000435660.5	TSL:1	c.58C>T	p.Arg20Trp	missense	Exon 2 of 13	ENSP00000399005.1	Q6NXT4-3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152124 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000239 AC: 6 AN: 251396 AF XY: 0.0000368

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.0000192 AC: 28 AN: 1461434 Hom.: 0 Cov.: 30 AF XY: 0.0000248 AC XY: 18 AN XY: 727030

African (AFR) AF: 0.0000598 AC: 2 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39616

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0000216 AC: 24 AN: 1111756

Other (OTH) AF: 0.0000331 AC: 2 AN: 60370

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152124 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74302

African (AFR) AF: 0.00 AC: 0 AN: 41408

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	Benign	0.11
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Benign	0.10
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.083	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.40	T
MutationAssessor	Benign	0.0	N
PhyloP100		5.3
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.37
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.088	T
Polyphen		0.31	B
Vest4		0.37
MutPred		0.42		Gain of catalytic residue at L18 (P = 0.016)
MVP		0.60
MPC		0.13
ClinPred		0.60	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.54
Mutation Taster		=73/27	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.22		Position offset: 32

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

Other links and lift over

dbSNP: rs764733512; hg19: chr2-32396410; COSMIC: COSV99250218;