2-32193948-C-T

Variant names:

• chr2-32193948-C-T
• rs771778692
• NM_017964.5:c.461C>T

Variant summary

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

The NM_017964.5(SLC30A6):​c.461C>T​(p.Ser154Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,212 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S154Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC30A6 NM_017964.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.09
• 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.461C>T	p.Ser154Phe	missense	Exon 8 of 14	NP_060434.2
	SLC30A6	NM_001193513.3		c.581C>T	p.Ser194Phe	missense	Exon 9 of 15	NP_001180442.1	Q6NXT4-2
	SLC30A6	NM_001193514.3		c.461C>T	p.Ser154Phe	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.461C>T	p.Ser154Phe	missense	Exon 8 of 14	ENSP00000282587.5	Q6NXT4-1
	SLC30A6	ENST00000379343.6	TSL:1	c.581C>T	p.Ser194Phe	missense	Exon 9 of 15	ENSP00000368648.2	Q6NXT4-2
	SLC30A6	ENST00000435660.5	TSL:1	c.461C>T	p.Ser154Phe	missense	Exon 8 of 13	ENSP00000399005.1	Q6NXT4-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461212 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726904

African (AFR) AF: 0.00 AC: 0 AN: 33452

American (AMR) AF: 0.00 AC: 0 AN: 44678

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39590

South Asian (SAS) AF: 0.00 AC: 0 AN: 86202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53340

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111710

Other (OTH) AF: 0.0000166 AC: 1 AN: 60358

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.028
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.76	N
PhyloP100		7.1
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.39
Sift	Benign	0.033	D
Sift4G	Benign	0.067	T
Polyphen		0.20	B
Vest4		0.85
MutPred		0.60		Loss of sheet (P = 0.0315)
MVP		0.38
MPC		0.031
ClinPred		0.90	D
GERP RS		5.7
Varity_R		0.47
gMVP		0.80
Mutation Taster		=31/69	disease causing

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

Other links and lift over

dbSNP: rs771778692; hg19: chr2-32419017;