5-69116004-G-T

Variant names:

• chr5-69116004-G-T
• rs371041170
• NM_022902.5:c.862G>T

Variant summary

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

The NM_022902.5(SLC30A5):​c.862G>T​(p.Val288Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC30A5 NM_022902.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.80

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]

ENSG00000248664 (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=0.37388262).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC30A5	NM_022902.5	c.862G>T	p.Val288Leu	missense_variant	Exon 9 of 16	ENST00000396591.8	NP_075053.2
SLC30A5	XM_005248569.4	c.739G>T	p.Val247Leu	missense_variant	Exon 8 of 15		XP_005248626.1
SLC30A5	XM_006714672.5	c.862G>T	p.Val288Leu	missense_variant	Exon 9 of 15		XP_006714735.1
SLC30A5	XM_017009749.2	c.739G>T	p.Val247Leu	missense_variant	Exon 8 of 14		XP_016865238.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC30A5	ENST00000396591.8	c.862G>T	p.Val288Leu	missense_variant	Exon 9 of 16	1	NM_022902.5	ENSP00000379836.3
SLC30A5	ENST00000507354.5	n.1060G>T		non_coding_transcript_exon_variant	Exon 6 of 11	1
ENSG00000248664	ENST00000504129.1	n.609-602C>A		intron_variant	Intron 4 of 5	5
ENSG00000248664	ENST00000690195.2	n.683-602C>A		intron_variant	Intron 4 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251234 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135786

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461756 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727192

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.17
Sift	Benign	0.090	T
Sift4G	Benign	0.10	T
Polyphen		0.83	P
Vest4		0.56
MutPred		0.23		Gain of loop (P = 0.069);
MVP		0.62
MPC		0.69
ClinPred		0.52	D
GERP RS		4.8
Varity_R		0.16
gMVP		0.74

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: rs371041170; hg19: chr5-68411831;