chr5-69115243-G-C

Variant names:

• chr5-69115243-G-C
• rs1746334489
• NM_022902.5:c.619G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_022902.5(SLC30A5):​c.619G>C​(p.Val207Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V207I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC30A5 NM_022902.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.77
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• cardiomyopathy

  Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia
• dilated cardiomyopathy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000248664 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.752

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022902.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC30A5	NM_022902.5	MANE Select	c.619G>C	p.Val207Leu	missense	Exon 8 of 16	NP_075053.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC30A5	ENST00000396591.8	TSL:1 MANE Select	c.619G>C	p.Val207Leu	missense	Exon 8 of 16	ENSP00000379836.3	Q8TAD4-1
	SLC30A5	ENST00000507354.5	TSL:1	n.817G>C		non_coding_transcript_exon	Exon 5 of 11
	SLC30A5	ENST00000862257.1		c.619G>C	p.Val207Leu	missense	Exon 8 of 16	ENSP00000532316.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.034	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-0.40	T
MutationAssessor	Benign	1.6	L
PhyloP100		9.8
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.23
Sift	Benign	0.21	T
Sift4G	Benign	0.24	T
Polyphen		0.83	P
Vest4		0.79
MutPred		0.28		Gain of ubiquitination at K204 (P = 0.078)
MVP		0.80
MPC		0.69
ClinPred		0.79	D
GERP RS		5.5
Varity_R		0.27
gMVP		0.76
Mutation Taster		=41/59	disease causing

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

Other links and lift over

dbSNP: rs1746334489; hg19: chr5-68411070;