Genetic Variant SLC30A6:p.Tyr92His (chr2-32184328-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_017964.5(SLC30A6):c.274T>C(p.Tyr92His) variant causes a missense change. The variant allele was found at a frequency of 0.0000466 in 1,500,918 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 0.00022 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

SLC30A6
NM_017964.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.00

Publications

2 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.21334445).

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.274T>C	p.Tyr92His	missense	Exon 5 of 14	NP_060434.2
SLC30A6	NM_001193513.3		c.394T>C	p.Tyr132His	missense	Exon 6 of 15	NP_001180442.1	Q6NXT4-2
SLC30A6	NM_001193514.3		c.274T>C	p.Tyr92His	missense	Exon 5 of 13	NP_001180443.1	Q6NXT4-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC30A6	ENST00000282587.9	TSL:1 MANE Select	c.274T>C	p.Tyr92His	missense	Exon 5 of 14	ENSP00000282587.5	Q6NXT4-1
SLC30A6	ENST00000379343.6	TSL:1	c.394T>C	p.Tyr132His	missense	Exon 6 of 15	ENSP00000368648.2	Q6NXT4-2
SLC30A6	ENST00000435660.5	TSL:1	c.274T>C	p.Tyr92His	missense	Exon 5 of 13	ENSP00000399005.1	Q6NXT4-3

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000699

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000558

AC:

AN:

214870

AF XY:

0.0000597

show subpopulations

Gnomad AFR exome

AF:

0.000588

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:

0.0000393

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000267

AC:

AN:

1348674

Hom.:

Cov.:

AF XY:

0.0000284

AC XY:

AN XY:

667886

show subpopulations

African (AFR)

AF:

0.000398

AC:

AN:

30114

American (AMR)

AF:

0.00

AC:

AN:

36428

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23406

East Asian (EAS)

AF:

0.00

AC:

AN:

36284

South Asian (SAS)

AF:

0.00

AC:

AN:

66126

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49082

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5298

European-Non Finnish (NFE)

AF:

0.0000162

AC:

AN:

1047052

Other (OTH)

AF:

0.000128

AC:

AN:

54884

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

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

AF:

0.000223

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.000699

AC:

AN:

41470

American (AMR)

AF:

0.000196

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5208

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68044

Other (OTH)

AF:

0.00

AC:

AN:

2090

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

Genome 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

Alfa

AF:

0.000250

Hom.:

Bravo

AF:

0.000253

ESP6500AA

AF:

0.000682

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Uncertain

0.028

BayesDel_noAF

Pathogenic

0.17

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.095

Eigen

Benign

0.011

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.024

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.7

PhyloP100

6.0

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-2.6

REVEL

Uncertain

0.38

Sift

Benign

0.10

Sift4G

Benign

0.18

Polyphen

0.24

Vest4

0.84

MVP

0.20

MPC

0.041

ClinPred

0.12

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.24

gMVP

0.59

Mutation Taster

=57/43

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over