5-69115369-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_022902.5(SLC30A5):c.745T>G(p.Leu249Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC30A5 NM_022902.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.721

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4196988).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC30A5	NM_022902.5	c.745T>G	p.Leu249Val	missense_variant	8/16	ENST00000396591.8
SLC30A5	XM_005248569.4	c.622T>G	p.Leu208Val	missense_variant	7/15
SLC30A5	XM_006714672.5	c.745T>G	p.Leu249Val	missense_variant	8/15
SLC30A5	XM_017009749.2	c.622T>G	p.Leu208Val	missense_variant	7/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC30A5	ENST00000396591.8	c.745T>G	p.Leu249Val	missense_variant	8/16	1	NM_022902.5	P1
SLC30A5	ENST00000507354.5	n.943T>G		non_coding_transcript_exon_variant	5/11	1
	ENST00000690195.2	n.716A>C		non_coding_transcript_exon_variant	5/6
	ENST00000504129.1	n.642A>C		non_coding_transcript_exon_variant	5/6	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 21, 2022

The c.745T>G (p.L249V) alteration is located in exon 8 (coding exon 8) of the SLC30A5 gene. This alteration results from a T to G substitution at nucleotide position 745, causing the leucine (L) at amino acid position 249 to be replaced by a valine (V). 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	Benign	0.32
BayesDel_addAF	Uncertain	0.096	D
BayesDel_noAF	Benign	-0.10
Cadd	Benign	20
Dann	Uncertain	1.0
DEOGEN2	Benign	0.40	T
Eigen	Benign	0.024
Eigen_PC	Benign	-0.059
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.52	T
MutationAssessor	Uncertain	2.4	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.31
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.034	D
Polyphen		0.99	D
Vest4		0.46
MutPred		0.28		Gain of sheet (P = 0.0028);
MVP		0.58
MPC		0.95
ClinPred		0.87	D
GERP RS		-0.98
Varity_R		0.064
gMVP		0.63

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: rs1329181745; hg19: chr5-68411196;