Genetic Variant NM_017964.5:c.582C>G (chr2-32197743-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017964.5(SLC30A6):c.582C>G(p.Phe194Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLC30A6
NM_017964.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.374

Publications

0 publications found

Variant links:

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]

SLC30A6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09185231).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC30A6	NM_017964.5	MANE Select	c.582C>G	p.Phe194Leu	missense	Exon 10 of 14	NP_060434.2
SLC30A6	NM_001330477.2		c.-10C>G		5_prime_UTR_premature_start_codon_gain	Exon 9 of 13	NP_001317406.1	B3KU87
SLC30A6	NM_001330478.2		c.-10C>G		5_prime_UTR_premature_start_codon_gain	Exon 6 of 10	NP_001317407.1	B3KU87

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC30A6	ENST00000282587.9	TSL:1 MANE Select	c.582C>G	p.Phe194Leu	missense	Exon 10 of 14	ENSP00000282587.5	Q6NXT4-1
SLC30A6	ENST00000379343.6	TSL:1	c.702C>G	p.Phe234Leu	missense	Exon 11 of 15	ENSP00000368648.2	Q6NXT4-2
SLC30A6	ENST00000435660.5	TSL:1	c.582C>G	p.Phe194Leu	missense	Exon 10 of 13	ENSP00000399005.1	Q6NXT4-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461786

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727190

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39680

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111960

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Benign

-0.071

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.0042

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.45

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.0086

MetaRNN

Benign

0.092

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.4

PhyloP100

0.37

PrimateAI

Uncertain

0.70

PROVEAN

Benign

0.49

REVEL

Benign

0.17

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0020

Vest4

0.35

MutPred

0.46

Gain of helix (P = 0.132)

MVP

0.20

MPC

0.031

ClinPred

0.42

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.080

gMVP

0.68

Mutation Taster

=65/35

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over