rs869320722

Positions:

• chr20-3230596-GCGTA-GT

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1 PM2 PM4_Supporting PP3 PP5

The NM_001174089.2(SLC4A11):​c.1330_1333delinsA​(p.Tyr444_Ala445delinsThr) variant causes a protein altering 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). Synonymous variant affecting the same amino acid position (i.e. Y444Y) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: SLC4A11 NM_001174089.2 protein_altering
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.25

Genes affected

SLC4A11 (HGNC:16438): (solute carrier family 4 member 11) This gene encodes a voltage-regulated, electrogenic sodium-coupled borate cotransporter that is essential for borate homeostasis, cell growth and cell proliferation. Mutations in this gene have been associated with a number of endothelial corneal dystrophies including recessive corneal endothelial dystrophy 2, corneal dystrophy and perceptive deafness, and Fuchs endothelial corneal dystrophy. Multiple transcript variants encoding different isoforms have been described. [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PM1: In a transmembrane_region Helical (size 23) in uniprot entity S4A11_HUMAN there are 5 pathogenic changes around while only 1 benign (83%) in NM_001174089.2
• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001174089.2. Strenght limited to Supporting due to length of the change: 1aa.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• PP5: Variant 20-3230597-CGTA-T is Pathogenic according to our data. Variant chr20-3230597-CGTA-T is described in ClinVar as [Pathogenic]. Clinvar id is 1313.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC4A11	NM_001174089.2	c.1330_1333delinsA	p.Tyr444_Ala445delinsThr	protein_altering_variant	12/20	ENST00000642402.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC4A11	ENST00000642402.1	c.1330_1333delinsA	p.Tyr444_Ala445delinsThr	protein_altering_variant	12/20		NM_001174089.2	P2

Frequencies

GnomAD3 genomes Cov.: 34

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

GnomAD4 genome Cov.: 34

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Corneal dystrophy-perceptive deafness syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

May 01, 2007

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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: rs869320722; hg19: chr20-3211243;