1-100913666-A-C

Variant names:

• chr1-100913666-A-C
• rs372301787
• NM_133496.5:c.515A>C

Variant summary

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

The NM_133496.5(SLC30A7):​c.515A>C​(p.His172Pro) variant causes a missense change. 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. H172R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC30A7 NM_133496.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.20
• Publications: 0 publications found

Genes affected

SLC30A7 (HGNC:19306): (solute carrier family 30 member 7) Zinc functions as a cofactor for numerous enzymes, nuclear factors, and hormones and as an intra- and intercellular signal ion. Members of the zinc transporter (ZNT)/SLC30 subfamily of the cation diffusion facilitator family, such as SLC30A7, permit cellular efflux of zinc (Seve et al., 2004 [PubMed 15154973]).[supplied by OMIM, Mar 2008]

SLC30A7 Gene-Disease associations (from GenCC):

• Joubert syndrome

  Inheritance: AD Classification: LIMITED Submitted by: G2P

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, 0.797

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC30A7	NM_133496.5	c.515A>C	p.His172Pro	missense_variant	Exon 6 of 11	ENST00000357650.9	NP_598003.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC30A7	ENST00000357650.9	c.515A>C	p.His172Pro	missense_variant	Exon 6 of 11	1	NM_133496.5	ENSP00000350278.4
SLC30A7	ENST00000370112.8	c.515A>C	p.His172Pro	missense_variant	Exon 6 of 12	1		ENSP00000359130.4
SLC30A7	ENST00000850622.1	n.515A>C		non_coding_transcript_exon_variant	Exon 6 of 13			ENSP00000520907.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.61	D;D
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.86	.;D
M_CAP	Benign	0.072	D
MetaRNN	Pathogenic	0.80	D;D
MetaSVM	Benign	-0.42	T
MutationAssessor	Pathogenic	3.1	M;M
PhyloP100		7.2
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-4.6	D;D
REVEL	Uncertain	0.59
Sift	Benign	0.13	T;T
Sift4G	Uncertain	0.0030	D;D
Polyphen		0.47	P;P
Vest4		0.82
MutPred		0.45		Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);
MVP		0.79
MPC		0.47
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.82
gMVP		0.53
Mutation Taster		=13/87	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: rs372301787; hg19: chr1-101379222;