Variant 5-69115957-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_022902.5(SLC30A5):c.815T>A(p.Met272Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000958 in 1,461,336 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

SLC30A5
NM_022902.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.99

Variant links:

Genes affected

SLC30A5 (HGNC:19089): (solute carrier family 30 member 5) This gene encodes a member of the SLC30A/ZnT family of zinc transporter proteins. ZnT proteins mediate both cellular zinc efflux and zinc sequestration into membrane-bound organelles. The encoded protein plays a role in the early secretory pathway as a heterodimer with zinc transporter 6, and may also regulate zinc sequestration into secretory granules of pancreatic beta cells. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 19. [provided by RefSeq, Oct 2011]

SLC30A5 links:

ENSG00000248664 (HGNC:):

ENSG00000248664 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.763

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC30A5	NM_022902.5 link	c.815T>A	p.Met272Lys	missense_variant	Exon 9 of 16	ENST00000396591.8	NP_075053.2	Q8TAD4-1
SLC30A5	XM_005248569.4 link	c.692T>A	p.Met231Lys	missense_variant	Exon 8 of 15		XP_005248626.1
SLC30A5	XM_006714672.5 link	c.815T>A	p.Met272Lys	missense_variant	Exon 9 of 15		XP_006714735.1
SLC30A5	XM_017009749.2 link	c.692T>A	p.Met231Lys	missense_variant	Exon 8 of 14		XP_016865238.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC30A5	ENST00000396591.8 link	c.815T>A	p.Met272Lys	missense_variant	Exon 9 of 16	1	NM_022902.5	ENSP00000379836.3	Q8TAD4-1
SLC30A5	ENST00000507354.5 link	n.1013T>A		non_coding_transcript_exon_variant	Exon 6 of 11	1
ENSG00000248664	ENST00000504129.1 link	n.609-555A>T		intron_variant	Intron 4 of 5	5
ENSG00000248664	ENST00000690195.2 link	n.683-555A>T		intron_variant	Intron 4 of 5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000800

AC:

AN:

250030

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135216

show subpopulations

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 SAS exome

AF:

0.0000655

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1461336

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

726994

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000720

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.815T>A (p.M272K) alteration is located in exon 9 (coding exon 9) of the SLC30A5 gene. This alteration results from a T to A substitution at nucleotide position 815, causing the methionine (M) at amino acid position 272 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Uncertain

0.027

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.22

Eigen

Benign

0.15

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.030

MetaRNN

Pathogenic

0.76

MetaSVM

Benign

-0.74

MutationAssessor

Benign

1.9

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.8

REVEL

Benign

0.26

Sift

Benign

0.067

Sift4G

Uncertain

0.026

Polyphen

0.29

Vest4

0.88

MutPred

0.63

Gain of ubiquitination at M272 (P = 0.03);

MVP

0.51

MPC

0.71

ClinPred

0.26

GERP RS

5.5

Varity_R

0.45

gMVP

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over