chr1-100912217-CA-AG

Position:

• chr1-100912217-CA-AG

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PS1 PM2 PP3 PP5

The NM_133496.5(SLC30A7):​c.490_491delCAinsAG​(p.His164Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin Lovd.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC30A7 NM_133496.5 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 8.62

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 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

• PS1: Transcript NM_133496.5 (SLC30A7) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in Lovd
• PM2: Very rare variant in population databases, with high coverage
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• PP5: Variant 1-100912217-CA-AG is Pathogenic according to our data. Variant chr1-100912217-CA-AG is described in ClinVar as [Pathogenic]. Clinvar id is 375382.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC30A7	NM_133496.5	c.490_491delCAinsAG	p.His164Ser	missense_variant		ENST00000357650.9	NP_598003.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC30A7	ENST00000357650.9	c.490_491delCAinsAG	p.His164Ser	missense_variant		1	NM_133496.5	ENSP00000350278.4
SLC30A7	ENST00000370112.8	c.490_491delCAinsAG	p.His164Ser	missense_variant		1		ENSP00000359130.4

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Joubert syndrome 1 Pathogenic:1

Pathogenic, no assertion criteria provided

research

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

-

This variant was identified in an individual with a clinical diagnosis of Joubert syndrome. -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1057519442; hg19: chr1-101377773;