chr20-3230597-CGTA-T

Variant names:

• chr20-3230597-CGTA-T
• rs869320722
• NM_001174089.2:c.1330_1333delTACGinsA

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2 PM4_Supporting PP3 PP5

The NM_001174089.2(SLC4A11):​c.1330_1333delTACGinsA​(p.Tyr444_Ala445delinsThr) variant causes a missense, conservative inframe deletion 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 missense, conservative_inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.25
• Publications: 0 publications found

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]

SLC4A11 Gene-Disease associations (from GenCC):

• corneal dystrophy, Fuchs endothelial, 4

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
• congenital hereditary endothelial dystrophy of cornea

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
• corneal dystrophy-perceptive deafness syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia
• Fuchs' endothelial dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

• 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 VariationId is 1313.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001174089.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A11	NM_001174089.2	MANE Select	c.1330_1333delTACGinsA	p.Tyr444_Ala445delinsThr	missense conservative_inframe_deletion	Exon 12 of 20	NP_001167560.1
	SLC4A11	NM_001174090.2		c.1459_1462delTACGinsA	p.Tyr487_Ala488delinsThr	missense conservative_inframe_deletion	Exon 12 of 20	NP_001167561.1
	SLC4A11	NM_032034.4		c.1378_1381delTACGinsA	p.Tyr460_Ala461delinsThr	missense conservative_inframe_deletion	Exon 11 of 19	NP_114423.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A11	ENST00000642402.1	MANE Select	c.1330_1333delTACGinsA	p.Tyr444_Ala445delinsThr	missense conservative_inframe_deletion	Exon 12 of 20	ENSP00000493503.1
	SLC4A11	ENST00000380056.7	TSL:1	c.1378_1381delTACGinsA	p.Tyr460_Ala461delinsThr	missense conservative_inframe_deletion	Exon 11 of 19	ENSP00000369396.3
	SLC4A11	ENST00000380059.7	TSL:2	c.1459_1462delTACGinsA	p.Tyr487_Ala488delinsThr	missense conservative_inframe_deletion	Exon 12 of 20	ENSP00000369399.3

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

ClinVar submissions as Germline

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Corneal dystrophy-perceptive deafness syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.3
Mutation Taster		=1/199	disease causing

Splicing

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

Other links and lift over

dbSNP: rs869320722; hg19: chr20-3211243;