dbSNP rs767603147: SLC30A7:p.Leu30Gln (chr1-100896578-T-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3BS2

The NM_133496.5(SLC30A7):c.89T>A(p.Leu30Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,461,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. L30P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

SLC30A7
NM_133496.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.21

Publications

1 publications found

Variant links:

Genes affected

SLC30A7 (HGNC:19306): (solute carrier family 30 member 7) Zinc functions as a cofactor for numerous enzymes, nuclear factors, and hormones and as an intra- and intercellular signal ion. Members of the zinc transporter (ZNT)/SLC30 subfamily of the cation diffusion facilitator family, such as SLC30A7, permit cellular efflux of zinc (Seve et al., 2004 [PubMed 15154973]).[supplied by OMIM, Mar 2008]

SLC30A7 Gene-Disease associations (from GenCC):

Joubert syndrome
Inheritance: AD Classification: LIMITED Submitted by: G2P

SLC30A7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.828

BS2

High AC in GnomAdExome4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC30A7	NM_133496.5 link	c.89T>A	p.Leu30Gln	missense_variant	Exon 2 of 11	ENST00000357650.9	NP_598003.2	Q8NEW0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC30A7	ENST00000357650.9 link	c.89T>A	p.Leu30Gln	missense_variant	Exon 2 of 11	1	NM_133496.5	ENSP00000350278.4	Q8NEW0
SLC30A7	ENST00000370112.8 link	c.89T>A	p.Leu30Gln	missense_variant	Exon 2 of 12	1		ENSP00000359130.4	Q8NEW0
SLC30A7	ENST00000850622.1 link	n.89T>A		non_coding_transcript_exon_variant	Exon 2 of 13			ENSP00000520907.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1461710

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727154

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000135

AC:

AN:

1111874

Other (OTH)

AF:

0.0000331

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.030

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.56

D;D

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Benign

0.72

LIST_S2

Uncertain

0.95

.;D

M_CAP

Uncertain

0.11

MetaRNN

Pathogenic

0.83

D;D

MetaSVM

Benign

-0.60

MutationAssessor

Benign

1.4

L;L

PhyloP100

7.2

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-4.2

D;D

REVEL

Uncertain

0.54

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.021

D;D

Polyphen

0.99

D;D

Vest4

0.73

MutPred

0.56

Gain of disorder (P = 0.009);Gain of disorder (P = 0.009);

MVP

0.77

MPC

0.31

ClinPred

1.0

GERP RS

5.6

PromoterAI

-0.0028

Neutral

(source)

Varity_R

0.85

gMVP

0.90

Mutation Taster

=43/57

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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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rs767603147

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over