5-69116143-C-T

Position:

• chr5-69116143-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022902.5(SLC30A5):​c.1001C>T​(p.Ala334Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC30A5 NM_022902.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.98

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14961687).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC30A5	NM_022902.5	c.1001C>T	p.Ala334Val	missense_variant	9/16	ENST00000396591.8	NP_075053.2
SLC30A5	XM_005248569.4	c.878C>T	p.Ala293Val	missense_variant	8/15		XP_005248626.1
SLC30A5	XM_006714672.5	c.1001C>T	p.Ala334Val	missense_variant	9/15		XP_006714735.1
SLC30A5	XM_017009749.2	c.878C>T	p.Ala293Val	missense_variant	8/14		XP_016865238.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC30A5	ENST00000396591.8	c.1001C>T	p.Ala334Val	missense_variant	9/16	1	NM_022902.5	ENSP00000379836.3
SLC30A5	ENST00000507354.5	n.1199C>T		non_coding_transcript_exon_variant	6/11	1
ENSG00000248664	ENST00000504129.1	n.609-741G>A		intron_variant		5
ENSG00000248664	ENST00000690195.2	n.683-741G>A		intron_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Aug 19, 2024

The c.1001C>T (p.A334V) alteration is located in exon 9 (coding exon 9) of the SLC30A5 gene. This alteration results from a C to T substitution at nucleotide position 1001, causing the alanine (A) at amino acid position 334 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	0.077
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.083	T
Eigen	Benign	-0.039
Eigen_PC	Benign	0.21
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.34	N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.062
Sift	Benign	0.32	T
Sift4G	Benign	0.38	T
Polyphen		0.0080	B
Vest4		0.32
MutPred		0.24		Gain of methylation at K333 (P = 0.031);
MVP		0.44
MPC		0.39
ClinPred		0.76	D
GERP RS		5.7
Varity_R		0.10
gMVP		0.38

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-68411970;