5-69116562-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_022902.5(SLC30A5):c.1241G>A(p.Ser414Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000687 in 1,456,448 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: SLC30A5 NM_022902.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.22

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]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10035595).
• BP6: Variant 5-69116562-G-A is Benign according to our data. Variant chr5-69116562-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2321125.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC30A5	NM_022902.5	c.1241G>A	p.Ser414Asn	missense_variant	10/16	ENST00000396591.8
SLC30A5	XM_005248569.4	c.1118G>A	p.Ser373Asn	missense_variant	9/15
SLC30A5	XM_006714672.5	c.1241G>A	p.Ser414Asn	missense_variant	10/15
SLC30A5	XM_017009749.2	c.1118G>A	p.Ser373Asn	missense_variant	9/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC30A5	ENST00000396591.8	c.1241G>A	p.Ser414Asn	missense_variant	10/16	1	NM_022902.5	P1
SLC30A5	ENST00000507354.5	n.1439G>A		non_coding_transcript_exon_variant	7/11	1
	ENST00000690195.2	n.683-1160C>T		intron_variant, non_coding_transcript_variant
	ENST00000504129.1	n.609-1160C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000408 AC: 1 AN: 244840 Hom.: 0 AF XY: 0.00000755 AC XY: 1 AN XY: 132370

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: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000168

GnomAD4 exome AF: 0.00000687 AC: 10 AN: 1456448 Hom.: 0 Cov.: 31 AF XY: 0.00000828 AC XY: 6 AN XY: 724354

Gnomad4 AFR exome AF: 0.000210

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000118

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 27, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	17
Dann	Benign	0.95
DEOGEN2	Benign	0.15	T;T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.076
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.83	T;D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;.
MutationTaster	Benign	0.59	N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.85	N;.
REVEL	Benign	0.085
Sift	Benign	0.77	T;.
Sift4G	Benign	0.62	T;T
Polyphen		0.024	B;.
Vest4		0.11
MutPred		0.31		Loss of phosphorylation at S414 (P = 0.0495);.;
MVP		0.43
MPC		0.36
ClinPred		0.22	T
GERP RS		4.9
Varity_R		0.076
gMVP		0.25

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

LitVar

Other links and lift over

dbSNP: rs781086034; hg19: chr5-68412389;